The present study was conducted to investigate the expression of apoptosis-related factors in peripheral blood mononuclear cells (PBMC) of patients with chronic hepatitis B and their correlation to clinical prognosis. Sixty-two patients that were diagnosed with chronic hepatitis B were admitted to Xuzhou Hospital from March 2015 to February 2016 and were enrolled as the observation group, while 60 healthy subjects who were examined in the health examination center were selected as the control group. The PBMC of patients were collected, and mRNA expression levels of the apoptotic molecules (FAS, CASP3, CASP8 and CASP9) were measured using real-time fluorescence quantitative PCR. The protein expression levels of apoptosis-related genes in the plasma were detected using enzyme-linked immunosorbent assay (ELISA) and the serum HBV-DNA was quantitatively measured using real-time fluorescence quantitative PCR. The mRNA and protein expression levels of FAS, CASP3, CASP8 and CASP9 in the observation group were significantly higher than those in the control group (P<0.05). The positive rate and log value of the copy amount of HBV DNA in the observation group were significantly higher than those in the control group (P<0.05). The Pearson correlation coefficient analysis showed that FAS, CASP3, CASP8 and CASP9 were positively correlated with HBV DNA (P<0.05). The mRNA expression levels of FAS, CASP3, CASP8 and CASP9 in patients with negative HBV-DNA were significantly lower than those with positive HBV-DNA (P<0.05). Apoptosis of PBMCs play an important role in the occurrence and development of chronic hepatitis B, and is closely correlated to the level of serum virus replication and prognosis.