Objective：To investigate the interaction between the polymorphisms of hepatitis B virus（HBV）-related CD8+ T cell in－hibitory genes and HBV mutations and its influence on the outcome of HBV infection. Methods：A total of 239 healthy controls，429 patients with spontaneous clearance，and 858 patients with chronic HBV infection were enrolled. A total of 28 tagging single nucleotide polymorphisms were selected from 5 CD8+ T cell inhibitory genes for genotyping. Direct sequencing was performed to determine HBV mutations. Results：The interactions between the polymorphisms of CD8+ T cell inhibitory genes（rs485618，rs4656942，and rs3766377 in CD244 and rs6746608 in BIM） and HBV mutations（T53C，A166C，T216C，A293G，A1762T，G1764A，and A1762T/G1764A） had a great influence on the risk of liver cirrhosis（LC） or hepatocellular carcinoma（HCC）. Similar results were obtained by multifactor dimensionality reduction analysis. Conclusion：The polymorphisms of CD244 and BIM genes might be involved in the regulation of immune selection of LC- or HCC-related HBV mutations，and the interactions between them may affect the progression of chronic HBV infection.