More than 170 million people worldwide are chronic HCV (Hepatitis C virus) carriers, and about 30% ofthem will develop progressive liver disease, such as cirrhosis and hepatocellular carcinoma. A combina-tion of pegylated interferon- with ribavirin, the standard treatment for HCV infection, has been effectivein fewer than 50% of patients infected with HCV genotype 1. A strong T cell response against the non-structural protein 3 (NS3) is important for recovery from acute HCV infection, and an early multi-specificCD4+ helper and CD8+ cytotoxic T cell response is critical for HCV clearance. In the present study, wesuccessfully constructed a genetically modified Bifidobacterium longum (B. longum) displaying recombi-nant HCV-NS3 peptides containing some CD4 and CD8 epitopes located in the HCV-NS3 region as an oralvaccine against chronic HCV infection. The oral administration of this vaccine could induce NS3-specificimmune responses in mice through intestinal mucosal immunity. Our findings suggest that this noveloral vaccine has great potential as a novel oral vaccine against chronic HCV infection.