Although interferon (IFN) therapy suppresses the development of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC), the relationship between response to previous IFN therapy and postoperative outcome has not been clarified in patients who underwent curative resection for HCC. Of 175 patients who underwent curative hepatic resection for HCV-related HCC, 24 patients had HCC detected after IFN therapy. 11 patients who had a biochemical response (a normalized alanine aminotransferase (ALT) activity with or without disappearance of serum HCV RNA) were classified as the response group, while 13 patients were classified as the non-response group because they had no decrease in their ALT activity and had persistence of serum HCV RNA. The non-IFN group included 151 patients who had not received previous IFN therapy. The clinicopathologic findings and surgical outcomes were compared among these three groups. The serum activities of the aspartate aminotransferase and ALT just before surgery were significantly lower in the response group than in the other groups. Although no significant differences were noted in the other clinicopathologic findings or the operation method among these groups, the tumor-free survival rate of the response group was significantly higher than that of the two other groups. By multivariate analysis, the response group had an independently lower risk for postoperative recurrence (risk ratio, 0.07; P=0.0072). Hepatic resection offers hope for low incidence of postoperative recurrence in patients with HCC, especially when previous IFN therapy has controlled their active hepatitis associated with HCV.