The Misfit explains to the grandmother that he doesn't know why he was locked up in jail. He says that the prison "head doctor" explained to him that it was "because I killed my daddy" but then the Misfit explains that his father died of influenza and was buried in the Mount Hopewell Baptist Cemetery. The implication is that the prison psychiatrist probably was psychoanalyzing the Misfit and wondering why he was a psychopath and probably came up with the theory that he hated his father and each time he killed someone, he was symbolically killing his father. By the way the Misfit reacts with such anger to the grandmother's talk of Jesus and praying, his father might have been a religious fanatic, perhaps that beat him or forced religion down his throat, and it could have made him "snap". The evidence of this is that the Misfit is careful to mention that his father is buried in a Baptist Cemetery, and he remembers the specific name of it, ironically called "Hopewell". So now, each time he kills someone, it is as if he is acting out his hatred of his father.
O'Connor leaves much to the reader's imagination in her stories because she believed the grotesque characters needed to unfold their stories on their own, without too much extraneous writing by her.
So, when the Misfit killed the grandmother, he could have been vicariously killing his father. Notice that when the grandmother touches him and calls him one of her babies, it is then that he jumps back and shoots her three times. So, this connection that the grandmother tries to make with him, on a human and spiritual level, could have been the final thing that set him off. It is clearly evident that the Misfit is a psychopath, so he could be "killing" his father each time he kills someone else.