Hepatitis C virus (HCV) is a leading cause of acute and chronic liver disease. About 180 million people are infected with HCV, which can lead to liver cirrhosis, hepatocellular carcinoma and consequently death. In addition to NS5B and NS3/4A protease inhibitor, NS5A was proved to be a promising target for the treatment of HCV. Several NS5A inhibitors such as BMS-790052 were launched recently and some were under clinical trials. We prepared a series of NS5A inhibitors possessing new scaffold and evaluated their activities against HCV cell lines. Among them, several compounds showed potent anti-HCV activity. Herein, we present anti-HCV activity of the hit compounds against various HCV genotypes and resistant strains mutated at L31V, Y93H of NS5A.