More than 50 years have passed since interferon (IFN) was discovered. Until now, the signaling pathway and function of IFN were basically elucidated. IFN has been clinically used for patients with hepatitis B virus (HBV) or hepatitis C virus (HCV). In Japan, pegylated IFN (PEG-IFN) is just approved for patients with HBV related chronic hepatitis. Also, the adding of direct-acting antiviral agents to the combination therapy with PEG-IFN plus ribavirin will improve anti-HCV effect. Another important effect of IFN is a suppression of hepatocarcinogenesis in patients with viral related chronic liver diseases. Maintenance therapy with low dose of PEG-IFN or IFN can improve the prognosis of patients with advanced hepatic fibrosis.