Although it's now been over eighty years since Of Mice and Men was first published, it has lost none of its ability to stir up controversy—even today, it remains one of the most frequently challenged literary classics. Indeed, this novel been controversial throughout the whole of its existence, albeit for very different reasons.

When Of Mice and Men was first published, many conservative groups and individuals objected to the book on the grounds that the topics it touched on—including, violence, poverty, murder, and sex—were too dark, mature, or depressing for students. Steinbeck was also accused by some of promoting anti-business or anti-capitalistic attitudes with his deeply sympathetic portrayal of downtrodden migrant farm workers during the Great Depression.

Another point of contention over the years has been the language used throughout the book, which many parents and school boards have deemed unsuitable for children. The dialogue in the book does contain a significant amount of profanity, and the characters also make frequent use of offensive outdated terms and racial slurs. In modern times, the book's language is perhaps the most common reason for it being banned or challenged.

Attempts have also been made to ban the book on the basis of its portrayal of marginalized groups such as women, the disabled, and people of color. Critics have argued that in characters such as Lennie, Crooks, and Curley's wife, Steinbeck endorses outdated stereotypes and prejudices that have no place in modern society and therefore shouldn't be explored in a classroom setting.