【Objective】 To study the level of occult hepatitis B virus methylation and replication related genes, and to explore the effect of the former on the latter. 【Methods】 The cases in control group (healthy control, n=3), occult hepatitis B group (occult HBV group, n=3) and hepatitis B group (HBV group, n=3) were detected by Illumina methylation 850k chip. The difference analysis, GO analysis and KEGG analysis were carried out. The methylation and virus replication related genes DNMT1, DNMT2, Dnmt3a and ZHX2 were screened for RT-PCR. 【Results】 The methylation level of occult HBV group and HBV group was significantly higher than that of the control group. Difference analysis showed that there were 1 050 differential methylation sites in occult HBV group with the methylation level greater than non-methylation level, and 1 340 differential methylation sites as the opposite compared with the control group. In HBV group, there were 1 008 differential methylation sites with methylation level greater than non-methylation level, and 1 242 differential methylation sites as the opposite. Go analysis showed that compared with the control group, the differential gene expression in occult HBV group and HBV group was significantly related to many anabolic processes in biological process (BP), cell composition (CC) and molecular function (MF). The enrichment analysis of KEGG pathway between the control group and the occult HBV group showed that the differential genes were mainly involved in adhesion junction, basal cell carcinoma, endometrial carcinoma, EB virus infection, hepatocellular carcinoma and other signal pathways. The enrichment analysis of KEGG pathway in occult HBV group and HBV group showed that the differential genes were mainly involved in AMPK signal pathway, cell cycle, endometrial cancer, hepatitis C, hepatocellular carcinoma and other signal pathways. DNMT1 and DNMT3a in occult HBV group and HBV group were significantly higher while ZHX2 was significantly lower than those in control group. 【Conclusion】 The methylation level of occult HBV group and HBV group increased significantly while ZHX2 decreased significantly. Hypermethylation inhibited the expression of ZHX2 and changed the replication of hepatitis B virus. Hepatitis B virus DNA methylation provides a theoretical basis for the replication mechanism of hepatitis B virus and a new method for the treatment of hepatitis B virus.