Background/Aims: The aim of this study was to evaluate whether IFN prevents the development of HCC in patients with chronic hepatitis C. Methodology: 103 patients with chronic hepatitis C received IFN and 30 control patients were enrolled in this study. Results: In 33 patients (32.0%) who received IFN, alanine aminotransferase (ALT) decreased to normal range and HCV RNA became negative (complete response: CR). In 7 patients (6.7%), ALT decreased to less than 50 IU/L or stayed within the normal range, but HCV RNA remained positive (biochemical response: BR). In 63 patients (61.1%) and 30 control patients, ALT did not change and HCV RNA remained positive (no response: NR). HCC developed in 5 (4.9%) of the 103 patients who received IFN and 7 (23.3%) of the control patients (p < 0.01). In 5 patients who developed HCC, the response to IFN was NR and no HCC developed in patients with CR or BR. In addition, 5-year cumulative rate of development of HCC in 63 IFN NR patients and in control was 7.9% and 23.3% (p < 0.05). Conclusions: IFN decreased the development of HCC in not only patients with CR or BR but also patients with NR.