Objective To investigate the change of the levels of transforming growth factor-β (TGF-β), interleukin-10 (IL-10), interleukin-17 (IL-17) and interleukin-21 (IL-21) in peripheral blood of acquired immune deficiency syndrome (AIDS) patients and its relationships with overlapping hepatitis B virus (HBV) infection, to provide reference for clinical treatment and prevention and control. Method AIDS patients (research group) and healthy people (control group) were selected, and the levels of TGF-β, IL-10, IL-17 and IL-21 in peripheral blood of all subjects were detected. Followed up for 1 year, the patients of the research group were divided into overlapping infection group and non-overlapping infection group according to the overlapping HBV infection, and the levels of the above factors in the two groups were compared, and the relationships between the levels of each factors and the overlapping HBV infection in AIDS patients were analyzed by multivariate Logistic regression analysis method. Result The levels of TGF-β and IL-10 in peripheral blood of the research group [(13.62±2.48)ng/ml and (6.61±1.29)pg/ml] were higher than those of the control group[(5.24±0.93)ng/ml and(1.96±0.38)pg/ml], while the levels of IL-17 and IL-21 [(26.41±5.07)pg/ml and (86.35±16.48)pg/ml] were lower than those of the control group[(58.23±10.16)ng/ml and(257.19±41.35)pg/ml], and the differences were statistically significant (t=40.588, 44.231, 37.671, 51.827, all P<0.001). Followed up for 1 years, the rate of overlapping HBV infection of AIDS patients was 13.44% (25/186). The levels of TGF-β and IL-10 in peripheral blood of the overlapping infection group [(16.75±3.22)ng/ml and (7.28±1.41)pg/ml] were higher than those of the non-over lapping infection group[(13.13±2.54)ng/ml and(6.51±1.26)pg/ml], while the levels of IL-17 and IL-21 [(23.06±4.48) pg/ml and (75.42±14.63) pg/ml] were lower than those of non-over lapping infection group[(26.93±5.04)pg/ml and(88.05±16.59)pg/ml], and the differences were statistically significant (t=6.382, 2.797, 3.622, 3.594, all P<0.05). Multivariate Logistic regression analysis showed that family history of HBV infection, poor coordination of AIDS treatment and the high TGF-β level and high IL-10 level in peripheral blood were all risk factors for overlapping HBV infection in AIDS patients (OR=3.842, 2.588, 3.615, 3.111, P<0.05), but hepatitis B vaccination history and IL-17 level and IL-21 level in peripheral blood were protective factors (OR=0.427, 0.520, 0.534, P<0.05). Conclusion The levels of TGF-β and IL-10 in peripheral blood of AIDS patients are abnormally increased, but the levels of IL-17 and IL-21 are abnormally decreased, and high levels of TGF-β and IL-10 can increases the risk of overlapping HBV infection in AIDS patients, while high levels of IL-17 and IL-21 can reduce the risk of overlapping HBV infection in AIDS patients.