Hepatitis C virus (HCV) is the etiological factor for Hepatitis C, which is one of the most important pathogenic factors of chronic liver diseases, cirrhosis and even hepatocellular carcinoma. HCV infection brings great threat to human health. Host genetic background could impact HCV infection, viral clearance, and treatment. Recently, some genome-wide association studies (GWAS) of HCV patients were performed. The results showed that single nucleotide polymorphisms (SNPs) of the IL28B gene, which encodes protein IFN-lambda3, are associated with viral clearance and treatment effectiveness of HCV patients who were cured by PEG-IFNalpha combined with ribavirin (RBV). IFN-lambda3 interacts with its acceptor, a heterodimer (IFN-lambdaR1 x IL-10R2), and upregulates the IFN-stimulated gene factors (ISGF). IFN-lambda3 plays roles in antiviral, antitumor, and immunoloregulation, and thus it might become a potential drug for Hepatitis C treatment. However, the mechanism of the IL28B gene in HCV infection and treatment is unclear, and further studies are needed to reveal the veils and provide theoretical basis for developing a new antiviral drug in clinic.