Due to the lack of efficient cell culture systems, animal models, the low amounts of viral antigens and RNA in infected tissues, knowledge about the replication mechanisms,especially the RNA-dependent RNA polymerase(RdRp) of hepatitis C virus(HCV) is poor.Based on analysis of amino acid sequence of HCV polyprotein and analogy to the closely related flaviviruses and pestviruses,it is assumed that NS5B may be the RdRp of HCV.By Baculovirus and E.coli expression system and in vitro RNA replication system,it was demonstrated that the de novo synthesis of RNA could be catalyzed by NS5B,which resembles other viral RdRp.The biochemical properties and the mutation-function relationships of RdRp of HCV were comprehensively reviewed,and the potential of NS5B as an important new target for antiviral therapy was also discussed.