Why is the theme loneliness in Of Mice and Men?

The life of an itinerant rancher during the Great Depression was a lonely one. Often, these men would move from job to job, never having a stable place to live nor having the ability to enjoy a permanent family. George explains this all to Lennie: 

Guys like us, that work on ranches, are the loneliest guys in the world. They got no fambly. They don’t belong no place. They come to a ranch an’ work up a stake and then they go into town and blow their stake, and the first thing you know they’re poundin’ their tail on some other ranch. They ain’t got nothing to look ahead to. 

George goes on to explain that he and Lennie can combat this plight. Instead of accepting this lonely lifestyle, they are determined to stay together. Their friendship and their dream of owning a farm help them get through such a lonely existence. Their story is, in part, a strategy of avoiding loneliness. 

Crooks is also a lonely character. He is ostracized from the other ranchers because he is black. He has his own separate bunk in the harness room. Because the other workers shun him, Crooks closely guards his own space. When Lennie comes in to talk with him, Crooks is initially overprotective of his space and wants to be left alone. But over the course of their conversation with Lennie and Candy, Crooks warms to them because he sees them as kindred, lonely spirits. Candy fears that, in his old age, he will eventually been deemed useless and thus will face a lonely time in finding a new job. Crooks and Candy warm to Lennie's dream of owning a farm because they think they would have a place there. They would be accepted. However, Curley's wife puts a stop to this conversation and scares Crooks into returning to his ostracized state. 

Curley's wife is also a lonely figure. She is is only woman on the ranch. She may have felt pressured into marrying Curley for financial security. But she is lonely and therefore she constantly seeks out companionship with the other men. She also laments her missed opportunity. She had a dream of being an actress. Lennie, Crooks, Candy, and Curley's wife all experience loneliness for different reasons. This is why it is such a significant theme in the book.