There are many small conflicts in Of Mice and Men, but the main conflict involves the struggle for survival, a struggle which is shared by most living things. Lennie could not survive by himself. George looks after him. So George's struggle for survival is twice as hard as it is for most men. They nearly got killed in Weed. They ate their late three cans of beans the night before they show up for work at the ranch. They nearly don't get the jobs they came all this way for because they make a bad impression on the boss. He could easily tell them he didn't want them. They make a bad impression because they arrive late, and the boss becomes suspicious of George because he does all the talking for Lennie. But they manage to get jobs that will provide the bare minimum for survival. They get bunks to sleep in, a roof over their heads, and food. There is no security and they have to work long hours in the hot sun lifting 100-pound sacks of barley onto wagons. When the barley is all harvested, chances are that they will get laid off. Why should the owner keep providing bed and board if there is nothing for them to do? They will have to hit the road again. And they will be competing with thousands of other homeless, desperate men who need food and shelter.
A couple of the other characters are worse off than George. Candy has only one hand, and he is getting old. Crooks has a broken body and the added handicap of being black. What kind of job could he find if they laid him off at this place? Both Candy and Crooks are living in dread of losing their jobs. There was very little assistance available for the destitute in those days. Steinbeck made this more dramatic when he wrote his masterpiece, The Grapes of Wrath. Hordes of men, women, and children came to California hoping to find work picking fruit. The children were going hungry, and there was nothing their parents could do for them. If they could get temporary jobs picking fruit, they had to work hard for very little pay. And they usually had to buy food from a company store which charged exorbitant prices.
Some of the men in Of Mice and Men were young and strong, but they could see their futures in men like Crooks and Candy. When they could no longer lift hundred-pound sacks and keep at it all day, they would be summarily discharged. There were always younger men to replace them. So the conflict might be described as one of man against man.
A struggle for existence naturally follows from the high rate at which all organic beings tend to increase. There is no exception to the rule that every organic being naturally increases at so high a rate, that if not destroyed, the earth would soon be covered by the progeny of a single pair.
Charles Darwin, The Origin of Species
The condition of man . . . is a condition of war of everyone against everyone.