Emergence of drug-resistant viruses, high cost and adverse side-effects associated with the standard therapy against hepatitis C virus (HCV) infection demonstrate the need for development of well tolerated and effective antivirals. We identified and chemically characterised the dehydrorotenoid boeravinone H, isolated from the herb Boerhaviadiffusa, as a new inhibitor of HCV entry. The compound significantly inhibits the binding and entry of hepatitis C-like particles (HCV-LPs) in hepatoma cells invitro with no apparent cytotoxicity. Boeravinone H inhibits the initial phase of HCV entry probably by acting directly on the viral particle. Importantly, the compound prevents HCV entry and infection in cell culture (exvivo). Thus, boeravinone H is a potential antiviral agent for the prevention and control of HCV infection.