This article contains speculative information. Please keep this in mind as you read it.
Throughout the series, Mrs. Puff is regularly shown to dislike SpongeBob, often saying he is an "unteachable" student. She continually tries to come up with ways to "get rid of him." This is similar to SpongeBob's relationship with Squidward.
In episodes such as "Boating School" and "No Free Rides," Mrs. Puff is seen to give up on teaching or trying to improve SpongeBob. In "No Free Rides," Mrs. Puff passes SpongeBob on his test, just to stop having to teach him, even though he did horribly. In "Boating School," instead of disqualifying SpongeBob from the test for cheating, she tries to get him to keep driving successfully so he can pass.
Mrs. Puff's most infamous interaction with SpongeBob is in the episode "Demolition Doofus." In this episode, she tries to get SpongeBob killed by entering him into a demolition derby. Instead of dying, SpongeBob's terrible driving skills allow him to win the derby, making Mrs. Puff more hysterical and depressed than ever, to the point where she herself tries to kill him.
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