Interferon monotherapy is considered to have limited effectiveness in patients with HCV of a high viral load. Here, we reported a 21-year old male of chronic hepatitis C with a high viral load of HCV genotype 1b. He received both peg-interferon α-2b plus ribavirin and peg-interferon α-2a plus ribavirin combination therapy. But there were no virological response. Nevertheless, after starting natural interferon α(human lymphoblastoid interferon (HLBI), Sumiferon; Dainippon Sumitomo Pharmaceutical Co., Osaka, Japan), he became HCV-RNA negative at 4 week. The therapy is continued and HCV-RNA negativity is sustained for over 40 weeks. Eradication of HCV might be expected. Natural IFN α contains more than 20 subtypes, and one or more of them may have therapeutic effect against HCV virus of this patient.