The negative signal provided by some co-inhibitory factors like PD-1 was associated with chronic hepatitis B infection induced-T cell exhaustion, but the correlation of CpG methylation of Pdcd1 gene with PD-1 expression and medical laboratory indicators in chronic hepatitis B infection has not been elucidated yet.Blood samples from 20 chronic hepatitis B infection (CHB) patients and 20 spontaneous clearance (SC) patients were collected. Percentages of PD-1-positive CD8 T cells were analyzed by flow cytometry. The percentage of CpG methylation at the Pdcd1 locus was analyzed by bisulfite sequencing. Student's t test, Pearson, Spearman's correlation and Mann-Whitney tests were used to analyze the statistics.Percentages of PD-1-positive CD8 T cells in the peripheral blood T cells were significantly higher in CHB patients group than SC group (p<0.001). The methylation level of Pdcd1 was significantly lower in CHB patients (p<0.001), and the methylation level of Pdcd1 was negatively correlated with PD-1 expression level in CD8 T cells (p<0.001) and hepatitis-B surface antigen (HBsAg) (p<0.001).Our study suggests that Pdcd1 methylation is correlated with PD-1 expression on CD8 T cells and correlated with HBsAg and alanine aminotransferase (ALT). The results may provide new ideas of anti-PD-1 inhibitors and the epigenetic regulators such as demethylation inhibitors could be more successful therapeutic strategies in hepatitis B infection patients.