Chronic hepatitis B (CHB) is a serious disease caused by the hepatitis B virus (HBV). CHB can lead to liver cirrhosis and hepatocellular carcinoma (HCC). Strong evidence for the effect of host genetics has been previously reported. Hence, the difference in host genetics might affect the various outcomes of HBV infection. Polymorphisms in genes encoding interferons (IFNs) and interferon receptors such as IFN-α, IFN-γ, IFN-λ, IFNAR1, IFNAR2, IL10R2/IL10RB, IFNGR1, and IFNGR2 have been reported to be responsible for susceptibility to CHB infection. In this review, the current information in the literature on the association between gene polymorphisms of IFNs and their receptors and chronic HBV infection is summarized. This information can be used to determine the risk for CHB infection and/or the development of liver cancer. In addition, the knowledge about genetic polymorphisms could be applied for prevention, treatment of HBV infections, and the development of new therapeutics for HBV patients.