The effect of interferon alpha in chronic viral hepatitis and common side effects are well known, but axonal polyneuropathy and hearing loss have been rarely reported. A 58-year-old woman was administered interferon alpha-2a (9 MU/3 times a week) and lamividin (100 mg daily) with the diagnosis of chronic hepatitis B. At the fifth month of the treatment gait disturbance and tinnitus developed. In her neurological examination tandem gait was ataxic on the right side. Cerebral magnetic resonance imaging performed to elucidate a probable cerebral pathology revealed nonspecific millimetric hyperintense lesions thought to be related with her hypertension anamnesis. Electroneuromyography demonstrated mild axonal polyneuropathy. The finding of pure-tone audiometry was sensorineural hearing loss in her left ear. Our diagnosis was axonal polyneuropathy and sensorineural type hearing loss as a side effect of interferon. In conclusion, the development of polyneuropathy and sensorineural hearing loss in the same patient may suggest autoimmunity as the cause of these side effects.