A 67-year-old man with hepatitis C virus infection and histological features of chronic active hepatitis was treated with human recombinant interferon alpha-2b. He responded successfully to interferon with normalization of serum alanine aminotransferase and continuous eradication of hepatitis C virus. However, 4.5 years after the end of interferon therapy, hepatocellular carcinoma, 20 mm in diameter, was detected by routine ultrasonographic screening. The patient underwent surgical treatment for resection of the hepatocellular carcinoma. The non-cancerous liver tissue was histologically normal. This suggests that patients who have shown a complete response to interferon therapy for chronic hepatitis C should be followed up closely.