Clarice Starling, an ambitious FBI trainee haunted by her troubled childhood, is pulled from her training by Jack Crawford, head of the Bureau's Behavioral Science Unit. She is assigned to interview Dr. Hannibal Lecter, a brilliant psychiatrist and cannibalistic serial killer, in hopes of gaining insights into the psychology of a then-active serial killer nicknamed "Buffalo Bill." Bill is known for kidnapping and skinning his female victims; the FBI believes Lectilecte's understanding of the criminal mind might help them capture this elusive murderer.

As Starling engages Lecter in a series of intense conversations, he offers cryptic clues in exchange for personal details about her own past. Their complex interactions form a game of psychological cat and mouse. As Starling deciphers Lecter's vague hints and unravels the puzzle, she grows closer to predicting Buffalo Bill's next move and discovering his true identity. Meanwhile, Bill has captured a new victim, and the stakes become increasingly personal and desperate for Starling as she works against time to prevent another killing.