Pegylated Interferon-alpha, combined with ribavirin, gives high sustained virological response in patients with hepatitis C virus, an important public health problem and one of the most frequent chronic infectious diseases worldwide. Though it has therapeutic benefits, treatment with IFN-alpha may be complicated by various side effects, especially symptoms of major depression and acute mania. Psychosis is a rare side effect, and its management usually includes discontinuation of IFN-alpha. We report a case of psychotic disorder that occurred during therapy with pegylated Interferon-alpha given associated with ribavirin. After good response to psychiatric treatment, it became possible to finish the anti-viral therapy.