Interferon (IFN) reduces the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CHC). However, HCC develops in the some patients who have achieved a sustained virological response (SVR). The aim of this study was to clarify the features and prognosis of SVR patients who developed HCC. Twenty-six patients who underwent curative hepatectomy for initial HCC after IFN therapy were closely investigated. Twenty patients who were seropositive for HCV-RNA (non-SVR), and a further 6 patients who achieved SVRs (SVR) were included. We analyzed the clinicopathological features, immunological expression levels of p53 and whether HCV-RNA is present in the excised liver. The liver functions of the SVR group were almost better than those of the non-SVR group. However, there was no significant difference in pathological features, surgical factors and prognosis between the groups. In one case with SVR out of eight specimens tested was HCV-RNA detected in the non-cancerous tissue. Immunohistochemistry revealed overexpression of p53 in eight HCCs (100%) from SVR patients. Recurrent HCC still developed after the curative hepatectomy, even if viral elimination had been successful. And molecular alterations in hepatocarcinogenesis of SVR patients might be different from those of CHC patients.