The impact of the SNP of PNPLA3 on interferon therapy and HCC development after interferon therapy is still undetermined for Japanese patients with chronic hepatitis C. The present study investigated the factors associated with HCC development after interferon therapy for Japanese patients with chronic hepatitis C, and is the first to clarify significant associations of the SNP of PNPLA3 with HCC development after interferon therapy. The gene discussed is PNPLA3; the disease is hepatocellular carcinoma.