How does the Great Depression affect Of Mice and Men?

The nearly tangible presence of the Great Depression in Steinbeck's Of Mice and Men affects both the overall plot structure of the story as well as Steinbeck's style.
Firstly, the historical reality of the Depression is accurately shown through Steinbeck's main characters of George and Lennie as well as the characters with whom they come into contact. Throughout the novella, George and Lennie discuss their need to travel to find work because work is so scarce, and they have to prove their worth to both The Boss, the owner of the ranch, and Slim, the understood leader of the ranch hands, demonstrating, too, the scarcity of money. Even small events in the plot such as the anecdote that The Boss once had a gallon of whiskey delivered to the ranch hands on Christmas demonstrates the economically destitute backdrop for the novella. Similarly, the dream that George and Lennie have to own and run their own place is described as something that is almost "too good to be true" because it would require more funds than seems attainable.
Because the Depression has severe consequences for the ways in which people can live their lives in the story, Steinbeck's characterization and language seem to mirror a similar depression. It's as if, because of the harsh economic times, Steinbeck's characters are intentionally stripped of all superfluity and are left with only the harsher aspects of their personalities, which they need to survive. All characters, with the possible exception of Slim, consistently demonstrate an overall frustration with their lives and take it out on others. For example, Curley is jealous, Crooks is bitter, and Carlson is angry. The dialogue throughout the novella, too, demonstrates a shortness and lack of depth.

Of Mice and Men was published in 1937 during the Great Depression, and it's this period of American history that provides the background against which the novel is set. One of the most serious economic consequences of the Depression was mass unemployment. Large numbers of men found it nigh impossible to find a job, and so they left their homes and communities to look for work elsewhere. Even then, the best that many could hope for was manual labor or seasonal work. This is the situation in which Lennie and George find themselves; they are migrant farm laborers, traveling from place to place in search of work. It is this world of economic insecurity and exploitation that is encapsulated by Steinbeck in Of Mice and Men.
One of the themes of the book is reality versus dreams. Most of the characters in the story harbor one kind of dream or another. Lennie and George want to have their own ranch; Curley's wife dreams of making it big in the movies. But both those dreams are ultimately destroyed by the harsh realities of life in Depression-era America. The Great Depression challenged as never before the whole idea of the American Dream, undermining its legitimacy as an inspiring national myth. In Of Mice and Men the Depression holds people back, prevents them from aspiring to something better in life. It acts as a means of reinforcing existing inequalities of race, wealth, and power. In this sense, the ranch in the Salinas Valley where the story is set provides us with a glimpse in microcosm of the wider social realities of the Great Depression in the United States as a whole.