Right in the beginning of the novella, the boss of the ranch treats Lennie harshly, because he is not speaking up. The boss noticed that there might be something wrong with Lennie. If George did not think quickly on his feet, he would not have gotten the job. Hence, this is the first case of discrimination.
The boss turned on George. “Then why don’t you let him answer? What you trying to put over?"
George broke in loudly, “Oh! I ain’t saying he’s bright. He ain’t. But I say he’s a God damn good worker. He can put up a four hundred pound bale."
The boss deliberately put the little book in his pocket. He hooked his thumbs in his belt and squinted one eye nearly closed. “Say—what you sellin’?
“I said what stake you got in this guy? You takin’ his pay away from him?” “No, ‘course I ain’t. Why ya think I’m sellin’ him out?” (pg. 12)
Arguably the greatest example of discrimination is when Curley picks on him for no other reason than his size and slowness of mind. At one point, Curley just wails him in the face and beats him until blood drips from Lennie. Lennie is helpless in the face of such brutality. Here is the text:
Lennie looked helplessly at George, and then he got up and tried to retreat. Curley was balanced and poised. He slashed at Lennie with his left, and then smashed down his nose with a right. Lennie gave a cry of terror. Blood welled from his nose. “George,” he cried. “Make ‘um let me alone, George.” He backed until he was against the wall, and Curley followed, slugging him in the face. Lennie’s hands remained at his sides; he was too frightened to defend himself. (pg. 31)
In conclusion, people treat Lennie harshly because he is not like others. In the end, George has to kill him, as his friend, because the world is too cruel for someone like Lennie.