To investigate association between immune cell-related cytokines and development of chronic hepatitis B (CHB). Patients with chronic hepatitis B virus (HBV) infection in immune tolerance (IT, n=30) and hepatitis B envelope antigen (HBeAg) positive CHB (n=250) were enrolled in the study. HBV virus, serological indicators, and plasma cytokine levels were detected at the time of enrollment. The results showed that there were significant differences in median age of patients (27 vs. 31y), alanine aminotransferase level (ALT, 29.85 vs 234.70 U/L), alanine aminotransferase level (AST, 23.40 vs. 114.90 U/L), HBsAg level (4.79 vs. 3.88 log10 IU/ml), HBeAg (1606.36 vs. 862.47 S/CO) and HBV DNA load (8.17 vs 6.71 log10 IU/ml) between IT and CHB groups (all P<0.01). The median values of Fms-like tyrosine kinase 3 ligand (FLT3-L), interferon-γ (IFN-γ), interleukin- 17A (IL-17A) and transforming growth factor- beta (TGF-β1) in IT group were significantly higher than those in CHB group (FLT3-L: 41.62 vs. 27.47 pg/ml; IFN-γ: 42.48 vs. 33.18 pg/ml; IL-17A: 15.66 vs. 8.90 pg/ml; TGF-β1: 4921.50 vs. 2234 pg/ml. All P<0.01). The median values of IFN-a2, TGF-β3 and IL-10 levels in IT group were significantly lower than those in CHB group (IFN-α2: 15.24 vs. 35.78 pg/ml, P=0.000; TGF-β3: 131.69 vs. 162.61 pg/ml, P=0.025; IL-10: 5.02 vs. 7.9 pg/ml, P=0.012). The multivariate logistic regression analysis indicated that TGF-β 1 (OR=0.999, 95% CI 0.999-1.000, P<0.001) and TGF-β2 levels (OR=1.008, 95%CI 1.004-1.012, P <0.001) were significantly associated with the incidence of CHB. The results suggest that TGF-β level might be an independent factor related to the occurrence of CHB.