Objective To determine the association of plasma estradiol (E2) and interleukin 12 (IL-12) levels with hepatitis C virus (HCV) infection outcomes in paid blood donors.Metbods Totally 199 participants were categorized into three groups,including 72 healthy controls,39 cases who had spontaneous clearance and 88 subjects with persistent HCV infection.We determined all participates' plasma E2concentration,IL-12 level and liver function.Results Multivariate logistic regression analysis showed that the history of full blood donation (P =0.040) and the history of plasma donation (P ＜0.001) were significantly associated with HCV infection.There were no statistically significant differences in the plasma E2 concentration and IL-12 level among the three groups (all P ＞ 0.05).Furthermore,the plasma E2 concentration was positively correlated with IL-12 level (r =0.672,P ＜ 0.001) among the population.Conclusion Paid blood donation is a risk factor of HCV infection.Although our study indicated that estradiol may positively regulate the expression of IL-12,its biological function and effects on IL-12 and HCV infection remains to be elucidated in further large and functional studies.