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This study described the prevalence and trend of HIV, hepatitis C virus (HCV) and syphilis among female sex workers (FSWs) in China, and we tried to identify the correlation between HIV, HCV and syphilis. Disparity of the epidemics were found between lower-tier and higher-tier FSWs.Background. Studies on the transmission of human immunodeficiency virus (HIV) and sexually transmitted diseases in female sex workers (FSWs) have been limited primarily to inferences drawn by focusing on defined geographical areas.Methods and Findings. This serial cross-sectional study was conducted in mainland China from 2008 through 2012. Data for 827 079 participants was analyzed. We classified venues such as karaoke bars and hotels as high tier and venues such as hair salons and barbershops, massage parlors, and other public outdoor venues as low tier based on the participants’ socioeconomic status. FSWs who worked at the venues and those who were present on the days of the survey were recruited.The prevalence of HIV decreased from 0.6% in 2008 to 0.3% in 2012, the syphilis prevalence ranged from 2.4% to 3.2% between 2008 and 2012, and hepatitis C virus (HCV) prevalence decreased from 0.9% in 2008 to 0.8% in 2012. Further, we found that HIV, syphilis, and HCV prevalence proportions were high in FSWs from low tiers.Conclusions. HIV, syphilis, and HCV prevalence among FSWs in our study decreased during the study period. Comprehensive intervention strategies, particularly those that focus on low-tier and older FSWs, are needed in order to decrease the disease burden in this population. [ABSTRACT FROM AUTHOR]