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[Background] Kleine-Levin syndrome (KLS) comprises a triad of symptoms, including hypersomnia, hyperphagia, and hypersexuality, which is a rare disoder almost exclusively confined to male adolescents.To date, the etiology of KLS is still unclear.However, some reports suggest an autoimmune cause for the syndrome.The objiective of the case reports provided an clinical evidence for the autoimmune hypothesis of KLS.[Methods] Clinical presentation and analysis of a 12-year-old boy who developed KLS after being treated with the hepatitis B vaccine.[Findings] The patient first experienced an episode that was mainly manifested as hypersomnia, aphasia, and other behavioral or mood disorders after vaccination.During the succeeding three months, the subject experienced two episodes of drowsiness and sleep.Electroencephalogram revealed a decreased non-REM stage Ⅲ sleep as well as periodic high-amplitude (1 Hz to 1.5 Hz) slow waves in the stage Ⅲ-Ⅳ sleep lasting 10 s to 50 s.He was given 18 mg of methylphenidate hydrochloride extended-release tablets (OROS MPH) in the morning as treatment.Two days later, his drowsiness significantly reduced.The boy has already stopped treatment for six months and has resumed his studies after eight months of OROS MPH treatment.[Interpretation] Although the association between KLS and the autoimmune cause was still unclear, the case provided here might be useful for clinical physicians to make a proper diagnosis with individual patients.