In order to explore whether Hepatitis B virus (HBV) can escape the body’s immunity by means of the anti-immune mechanism of tumor cells, this study used HBV to infect hepatocytes, and then explored the changes of the immune response of infected hepatocytes to the host. The transcriptional levels of Axin and PD-L1 in hepatocytes after HBV infection were analyzed by real-time fluorescence quantitative PCR, and it was found that HBV did not affect the transcriptional levels of Axin and PD-L1. Then, western blot was used to find that HBV could down-regulate Axin protein levels in hepatocytes and up-regulate PD-L1 protein levels. Further transfection of plasmid expressing HBV component protein in cells showed that HBx could down-regulate Axin protein expression in cells by western blot. Data correlation analysis and ubiquitin assay showed that Axin promoted pD-L1 ubiquitin proteasome degradation by increasing the expression of E3 ubiquitin ligase SPOP of PD-L1. Further studies on the ubiquitination of PD-L1 showed that Axin promoted the K48-dependent ubiquitination of PD-L1. Based on the above results, we believe that HBV may down-regulate Axin and SPOP protein levels through HBx, inhibit PD-L1 ubiquitination and degradation, and then escape the host immune response. This study reveals a new mechanism of HBV immune escape, lays a new foundation for the treatment of HBV, and promotes the development of anti-HBV drugs to a certain extent.