The title of the novel/novella comes from a poem by Robert Burns called "To a Mouse." In this poem, the speaker is addressing a mouse he's found in his field while plowing. He regrets that the plow has destroyed the mouse's home. The speaker is genuinely sorry, feeling that the mouse deserves life as much as he does: ". . . thy poor earth-born companion, / An' fellow-mortal!" The speaker tells the mouse that he (mouse) is not alone in making promising plans that end up in disaster:
But little Mouse, you are not alone,
In proving foresight may be vain:
The best laid schemes of mice and men
Go often awry,
And leave us nothing but grief and pain,
For promised joy!
There is certainly a connection here with the speaker's affection for the mouse and Lennie's affection for mice (and all animals) in Of Mice and Men. But the other connection is between the mouse in the poem with George and Lennie in the novel. Like the mouse, George and Lennie continue to make plans of having their own farm. This is their hope and dream, their "scheme." Like the mouse, these "best laid schemes" go "awry" and ends in disaster.
Another way of looking at the title Of Mice and Men is that the reference is to the feelings expressed by Robert Burns in his own poem, "To a Mouse." Burns was motivated by pity for the mouse, and Steinbeck's use of the title for his novelette seems to be suggesting that he feels pity for the characters he is describing and wants his readers to pity them too. That is Steinbeck's reason for telling the story. We should pity all of them because, like the mouse, they are homeless and helpless, subject to catastrophe at practically any moment. But Steinbeck is also suggesting by the use of Burns's title that we ourselves are all like these characters, we are all vulnerable to unforeseen disasters, and therefore we should identify with these people who are our "poor earth-born companions and fellow mortals." The pen is mightier than the sword. A great writer like John Steinbeck or Charles Dickens or Victor Hugo or Leo Tolstoy can change social conditions by changing people's hearts and minds.