We experienced six patients with resected hepatocellular carcinoma (HCC) following interferon (IFN) therapy. Hepatitis virus C-RNA in polymerase chain reaction was positive in all patients prior to the IFN therapy. HCV-RNA became negative in two patients following IFN therapy, and was re-positive at the time of detection of HCC. In histological studies prior to the IFN therapy, pre-cirrhosis was diagnosed in four out of six patients and chronic active hepatitis 2B (CAH2B) in one according to the Europian classification. In non-cancerous portion of the liver, cirrhosis developed in five patients, and CAH2B in one. There was no significant correlation among the interval of HCC detection following IFN therapy, tumor size, tumor location, and histological findings. Patients should be carefully followed up by serum alpha fetoprotein levels or ultrasonography of the liver during and following IFN therapy.