Interferon (INF) is an immunomodulatory agent that is widely prescribed for treatment of chronic viral diseases, some haematological cancers, solid tumors and multiple sclerosis. Most common side effects of interferon therapy are şu-like symptoms, mild elevations in hepatic enzymes, fatigue, anorexia and neuropsychiatric symptoms. According to our knowledge, in this article, we report the first adolescent suffering from INF-alpha induced psychosis during hepatitis B treatment. Through this case report, we wanted to draw attention of clinicians on this rare but challenging side effect. A 14-year-old boy presented to emergency psychiatric unit with suspiciousness, aggressive behaviors against his family, persecutory, mystic and grandiose delusions for two months comorbid with active chronic hepatitis B infection had been diagnosed. Before first psychiatric admission, he was under the treatment of lamuvidine 100 mg/day for 2 weeks and he had been treated with interferon alpha 2b (3 million U/ week, subcutaneously) for six months. In his first mental status examination, he was awake, alert and disoriented with place and time. His speech was very slow, disorganized by several blocks and incoherent. His affect was inappropriate and restricted. His psychomotor activity was reduced. He had auditory hallucinations, persecutory, mystic and grandiose delusions. According to family, his psychiatric symptoms were firstly seen 2 weeks after cessation of INF therapy. He had no any psychiatric and medical diseases except for chronic hepatitis B. His neurologic examination and laboratory findings were normal. He was diagnosed as “medication-induced psychosis”. Because of his hepatitis history, an antipsychotic, metabolized especially by kidney was preferred. He was started on amisulpride 200 mg/day and titrated to 800 mg/day. Also, he continued taking antiviral treatment at the same dosage. At the end of second week of hospitalization, his delusions and hallucinations were totally regressed. His affect was appropriate and his social interaction was very well. He was discharged on amisulpride 800 mg/day and lamivudine 100 mg/day after a hospitalization period of fifteen days. The case mentioned above was evaluated as a possible interferon-alpha associated psychosis because that the symptoms started approximately six months after INF treatment. Also, the absences of any organic causes, family psychiatric history and past psychiatric disease explaining psychosis have supported our opinion. Because interferon induced psychosis has been seen rarely, it could be overlooked by clinicians in comparison to its more common side effects. Moreover, this rare side effect may interrupt treatment of some important diseases such as hepatitis and malignancies. In conclusion, we suggest that patients should be observed carefully by clinicians in terms of psychiatric side effects especially psychosis during interferon treatment.