Lennie's death in Of Mice and Men is one of the most haunting and heartbreaking scenes in all of literature. In short, George kills his best friend to spare him from a worse fate. After Lennie accidentally kills Curley's wife, a lynch mob sets out in search of him. George is only able to reach Lennie before the mob because he knows Lennie will have fled to their designated meeting spot in the woods.

After discovering the body of Curley's wife and piecing together what happened, George initially hopes that they can resolve things peacefully, but Slim, acting as the voice of reason, reminds George that Curley will never let Lennie go unpunished:

George stepped close. “Couldn’ we maybe bring him in an’ they’ll lock him up? He’s nuts, Slim. He never done this to be mean.”
Slim nodded. “We might,” he said. “If we could keep Curley in, we might. But Curley’s gonna want to shoot ‘im. Curley’s still mad about his hand. An’ s’pose they lock him up an’ strap him down and put him in a cage. That ain’t no good, George.”

Though he loathes the idea of it, George ultimately realizes that all he can do is give Lennie a painless death, sparing him from a cruel and violent end at the hands of the mob. His choice in this final chapter is foreshadowed by Candy's remorseful remarks after letting Carlson put his beloved dog out of its misery: “I ought to of shot that dog myself, George. I shouldn’t ought to of let no stranger shoot my dog.”

After making it to the clearing where Lennie is hiding, George reassures Lennie that he's not in trouble, even as the sounds of the approaching mob can be heard. Wanting his friend to be at peace, he instructs Lennie to look out over the river and, at Lennie's request, reiterates their dreams of a farm:

“We’ll have a cow,” said George. “An’ we’ll have maybe a pig an’ chickens . . . an’ down the flat we’ll have a . . . little piece alfalfa—”
“For the rabbits,” Lennie shouted.
“For the rabbits,” George repeated.
“And I get to tend the rabbits.”
“An’ you get to tend the rabbits.”
Lennie giggled with happiness. “An’ live on the fatta the lan’.”
“Yes.”

While Lennie is happily distracted by the talk of their future plans, George quietly puts a shotgun to the back of his neck and kills him. Lennie's death is made all the more poignant by the fact that in killing Lennie, George has not only lost his closest companion but also lost his dreams for a better life. Without Lennie, George is now just like the other ranch hands—all alone and without any hope for the future.

Basically, the main reason George kills Lennie is to spare his friend from experiencing the torture of being lynched.

Toward the end of the story, Lennie kills Curley's wife by accident. Frightened by the implications of his actions, Lennie runs away. We later learn that he has gone to a designated spot he and George agreed upon, for when trouble strikes.

Meanwhile, Curley and the men find Curley's dead wife in the barn. For his part, Curley is furious. He exclaims that he will shoot Lennie in the "guts."

As Curley gets a lynch party together, Slim and George confer privately. They agree that Lennie is in desperate trouble. George suggests that Lennie could be "saved" if they just bring him in themselves. He thinks that Lennie might just get locked up.

However, Slim cautions that Curley is still furious and will do whatever he can to get at Lennie. He also voices his opinion that prison may cause Lennie great suffering. According to Slim, the authorities may not take Lennie's mental condition into consideration and may mistreat him.

George agrees. So, the main reason George kills Lennie is to spare his friend great suffering. The other reason is that there is little he can do to prevent Lennie from committing a similar crime in the future. So, to spare everyone suffering (including Lennie), George does the only compassionate thing he can do for his friend. He takes his gun and shoots Lennie in the neck.

At the end of the story, only Slim understands why George killed Lennie.

George kills Lennie by shooting him in the back of the head to save him from a more painful death at the hands of Curley, who has vowed to make him suffer for the death of his wife. George loves his friend Lennie, whom he has looked after faithfully, and he doesn't want Lennie to die horribly, especially since Lennie has unwittingly taken the life of Curley's wife in much the same way as he petted the puppy too hard or squeezed the mice to death. Lennie didn't know his own strength. When Curley's wife screamed, he didn't know how to make her stop except to do what he did, but he did not intend to kill her.

Curley, of course, is also looking for a way to achieve revenge for Lennie's crushing his hand, so he will definitely try to kill Lennie in the most cruel way possible. He says he will "gut shoot" him. George must save his friend by a mercy killing.

People believe that George killed Lennie for several reasons. Lennie accidentally killed Curley's wife in the barn earlier. When Curley's wife is killed, George knows that Curley will likely torture and kill Lennie. Lennie would not fare well in a prison setting, nor would he be able to defend himself if Curley or the other men attempted to hurt him. George knows that he has to kill Lennie in order to protect him. Additionally, when Candy's dog is sick another one of the men takes him out back and shoots him. Candy is very sad about the loss of his dog, but he tells George that what makes him the most upset is that he knows he should have shot his own dog himself. Looking back at this, George knows that he has to kill Lennie himself so that someone else does not. He feels that it is his responsibility and he would not want someone else to do it because he loves Lennie.

George kills Lennie for multiple reasons.

•       The reason most commonly offered is that he wants to save Lennie from being tortured by the pursuing lynch mob. This is probably valid, but it does not explain why he doesn’t help Lennie escape. Lennie is hiding on the bank of a shallow river. They could wade across and climb into the Gabilan Mountains. The lynch mob might never even think of looking for them up there. Even if the mob finally guessed they had fled into the mountains, George and Lennie would have too much of a head start, and it would soon be getting dark. According to Lennie, the mountains have many caves. A mob would have to search each cave, and in the meantime the fugitives could be getting farther away.
•         George didn’t intend to help Lennie escape. This is proved conclusively by the fact that he stole Carlson’s Luger from under his bunk at the ranch. He intended to kill Lennie as painlessly as possible. When he saw the body of Curley’s wife in the barn, he assumed, like all the other men, that Lennie had tried to rape her and had unintentionally killed her while they were struggling. George realizes that Lennie is becoming a menace to society and that he would probably kill other girls if allowed to live in freedom.
•         This is the first time Lennie has killed a human being (although he has killed lots of animals). George is in some danger of being charged as an accessory to second-degree homicide. He told Lennie where to hide if he got into trouble. If he tried to help his friend escape, he would definitely be an accessory to murder.
•         George feels guilty for the death of Curley’s wife. In fact, he really is guilty because he brought Lennie to that ranch and the girl would still be alive if he hadn’t brought Lennie there. He is Lennie’s caretaker. He is responsible for any kind of trouble Lennie gets into—and he is beginning to realize that Lennie is growing into more of a problem than he is competent to handle.
•         George wants to rid himself of a big burden. He can’t handle the stress anymore. When he kills Lennie with the Luger he has mixed feelings, which include pity, sorrow, and remorse, but also a vast relief. He frequently abuses Lennie verbally, telling the childish giant that he could enjoy a much happier life if only he were free of him. Lennie is a burden because he is always getting into trouble and also because he has to be watched all the time. Lennie has caused George to lose jobs, and jobs are hard to come by. Lennie almost got both of them lynched by assaulting a girl in Weed.
•         George is angry at Lennie. He feels sorry for Curley’s dead wife. She was just a dumb girl. She should have had a chance to live out her whole life and not have it snuffed out the way Lennie had killed his puppy and so many other small animals. George kills Lennie for the same reason that the lynch mob wants to kill him. George is really fed up with his companion.
•         George can’t turn Lennie over to the authorities with the hope that they would put him in an asylum. He doesn’t have the power to determine Lennie’s fate. If he could manage to get Lennie arrested rather than lynched, the authorities would be likely to charge Lennie with murder. There would be plenty of evidence that he had killed Curley’s wife, and there would be plenty of witnesses to testify that he was guilty. The motive would be attempted rape. Nobody saw what happened in the barn. Lennie would be incapable of defending himself, and he wouldn’t have much of a defense anyway. He wouldn’t let go of the girl, she started screaming and struggling, and he killed her.
•         Lennie is showing many signs of rebelling against George’s control. He lies to George, threatens to run away and live by himself, doesn’t follow George’s instructions, sometimes deliberately disobeys. (For example, George told him to have nothing to do with Curley’s wife.) George may be a little bit afraid of Lennie, and with good reason. A time might come when Lennie might “accidentally” kill his keeper.

Steinbeck was a realist. His characters are not all good or all bad. George shows his good side by looking after Lennie for a long time. He shows his darker side by verbally abusing Lennie, by wanting to be rid of him, and finally by executing him. Lennie himself seems like a gentle, likeable character—except that he kills everything he touches, including his little puppy. Lennie is developing an interest in sex, and because of his feeble mind and giant strength he is potentially a monster who needs to be destroyed.  Slim is probably the most faultless character in the story, but he is a member of the lynch mob. He wouldn’t be present at the ending if he hadn’t come along with the mob. And there is no indication that he had any intention of giving Lennie any kind of help.

I would like to add one more thought to my answer to the question, "Why did George kill Lennie?"

We might say that it was John Steinbeck who killed Lennie. The author wanted to write a story about the hard lives of itinerant farm workers in California. At the same time, he definitely intended to adapt his story into a stage play to be produced in New York. The play could only run for a couple of hours at most, with an intermission in between. Steinbeck must have figured that he had to cut his story short somehow, and Of Mice and Men is so short that the book seems flimsy and it is called a novelette. It hardly does justice to the theme of homeless drifters struggling to survive by traveling all over California and working like slaves in the vast fields. The author's way of cutting his story short was to have one of the principal characters kill the other one. Then, of course, Steinbeck had to invent a good reason for this. He also had to foreshadow the abrupt ending and make it seem like the point of the story. Probably the only reason he had two principal characters in the first place was because in a stage play most information is conveyed through dialogue. So he needed two men who would talk to each other. If Of Mice and Men had been more of a conventional novel, there might have been only one principal or viewpoint character, as in Huckleberry Finn, Great Expectations, The Catcher in the Rye, and many other novels.

The book was published in 1937 and the New York play was produced in the same year, proving that Steinbeck was thinking about the play while he was writing the novella or novelette. Except for the scenes by the river, everything in the book takes place in two very simple settings: a bunkhouse and a barn. This is another sign that Steinbeck wanted to make it easy to adapt his book to a stage play. The scenes by the river could be simulated with nothing more than a fake campfire lighted by a couple of colored globes. The stage play was evidently a low-budget production because the subject matter was experimental for New York and no one could tell whether it would be successful.

Both the book and the play were very successful. They made Steinbeck famous. What made them successful was that Steinbeck had a genius for writing dialogue. Good dialogue conveys information and also characterizes the speaker. The dialogue spoken by Crooks, Candy, Lennie, and Curley's wife demonstrates Steinbeck's special ability. Furthermore, he understood his subject, he was sincere, he really cared about people and was really concerned about their pain.

There are really many reasons why George kills Lennie. It is often explained that this is a "mercy killing." George supposedly wants to save Lennie from the lynch mob, who will make his death as painful as possible, whereas George knows how to kill him instantly and painlessly with Carlson's Luger because Carlson has demonstrated how to do this with Candy's dog. But this explanation is an oversimplification. George has realized that Lennie is becoming a menace to society. Twice the mentally retarded giant has been involved in what could be interpreted as rape attempts, once in Weed and once with Curley's wife in the barn. George can't be watching Lennie all the time, and Lennie gets into trouble when he isn't being watched. Then he lies about it.

George realizes that Lennie is morphing into a monster who attacks young girls and is capable of killing them if they struggle. But George is getting fed up with being a caretaker, as he states repeatedly throughout the book. Furthermore, George feels responsible for the death of Curley's wife. If George hadn't protected Lennie in Weed, Lennie would never have encountered Curley's wife. George is not only morally responsible, but he believes he could be considered an accessory after the fact to that girl's murder. He is also afraid the lynch mob might turn on him because he and Lennie are so closely associated. Just before the mob leaves the ranch to hunt for Lennie, 

...Curley called, "You George! You stick with us so we don't think you had nothin' to do with this."

Curley suspects that George knows where Lennie went to hide. That in itself could make George appear guilty as an accessory. If someone commits a murder and you tell him where to go and hide and you say you don't know where he is hiding--then that makes you appear partly responsible for the murder. In the first chapter George instructed Lennie about where to come and hide if he got into trouble. That indicates that George expected Lennie to commit some serious offense, which could be interpreted to make George an accessory before and after the fact. How would anyone know that George had told Lennie where to hide if he got into trouble? Lennie would probably tell them.

George would have gotten killed by the mob in Weed, too, if they had been able to catch him and Lennie--or him alone. George is kind enough to make some sacrifices for Lennie and Aunt Clara, but he is not idealistic enough to become a martyr. George is very angry at Lennie and fears for his own life. He wants to distance himself from this trouble-maker. He cares enough to want to execute Lennie by himself, but he believes, as do all the men in the lynch mob, that Lennie must die. If he left Lennie to the lynch mob, they would kill him in a horrible manner. If he could manage to help Lennie to escape and then turned him over to the law, Lennie would get convicted of murder and executed by hanging (which was the legal method of execution in California at the time). Lennie is really only guilty of accidental manslaughter, but he would be totally incapable of explaining that to anyone. If George helped Lennie escape and didn't turn him over to the law, he could expect repetitions of what happened with the girl in Weed and with Curley's wife in the barn.

The fact that George steals Carlson's Luger in the bunkhouse shows that he has made up his mind to kill Lennie by that point. What prompted his decision was the sight of the dead girl in the barn.

Curley's wife lay with a half-covering of yellow hay. And the meanness and the plannings and the discontent and the ache for attention were all gone from her face. She was very pretty and simple, and her face was sweet and young. Now her rouged cheeks and her reddened lips made her seem alive and sleeping very lightly. The curls, tiny little sausages, were spread on the hay behind her head, and her lips were parted.

In the novella Of Mice and Men, John Steinbeck (1902-1968) uses the literary technique of foreshadowing, with respect to the character of Lennie, who, not knowing his own strength, harms or kills the items or people that were objects of his affection.  Curley's wife is killed by Lennie when he attempts to quiet her -- and Curley vows revenge on Lennie, promising he will die horribly by being "gut-shot."  

George, although he loves his friend Lennie, shoots him in the back of the head as a mercy killing to avoid being brutally murdered by Curley.

George kills Lennie because he feels responsible for Lennie's actions. As Lennie's caretaker, he was not there when Lennie accidentally killed Curley's wife. George now feels that he has to shoot Lennie as a way of showing some responsibility for what Lennie has done.

Also, Curley has vowed to make Lennie suffer and George cannot bear to see this happen. The only solution is to kill Lennie before Curley finds him. Curley is cruel. He will make Lennie's final death one of agony. George knows this about Curley. He shoots Lennie out of compassion. He is saving Lennie from brutal treatment.

George figures that Curley will hang Lennie. He knows this is a terrible way to die. He would rather shoot Lennie and get him out of his chance at a gruesome death.

Should Curley not kill Lennie, Lennie would have to be locked away for the rest of his life. George realizes this would be tremendous suffering for Lennie. He shoots him to end his possibility of being locked away for life:

When George hears the men closing in on them, he tells Lennie to look across the river. As he describes for the last time the farm that he and Lennie have so long dreamed of, he lifts Carlson’s gun from his side pocket. With great difficulty he points it at the back of Lennie’s head, and as his hand shakes violently, George pulls the trigger.