In Steinbeck's Of Mice and Men, first published in 1937, George and Lennie are friends who were born in the same town. After Lennie's caretaker, his Aunt Clara, dies, George and Lennie travel around together and eventually become inseparable.
They end up working together on a barley farm near Soledad, California, and while there Lennie accidentally kills the wife of Curley, whose father owns the farm.
George realizes that Curley will gather together a group of men to hunt Lennie down and kill him. So, George manages to steal Carlson's Luger pistol and find Lennie before Curley and the other men do. As George tells Lennie about their "dream" farm, George shoots Lennie in the back of the head. When Slim finds George, he tells him, "You hadda, George. I swear you hadda."
So, in a literal sense, George is guilty of killing Lennie because he pulled the trigger of the gun. Otherwise, I'm not sure what sort of guilt the question is referring to, unless the reader wants to fault George for not being with Lennie in the barn when Lennie accidentally killed Curley's wife.