To examine the prevalence of HIV, syphilis, and hepatitis C virus (HCV) infections by demographic characteristics and identify the subgroups of female sex workers (FSW) who are at a higher risk of the infections. Secondary analysis of the 2010 National Sentinel Surveillance (NSS) data was conducted in the current study. A total of 12,622 FSW recruited from 35 NSS sites in Guangxi, China were included in the analysis. FSW were tested for HIV, syphilis, and HCV. The overall prevalence of HIV, syphilis, and HCV infections were 1.0%, 6.1% and 1.0%, respectively. The prevalence of HIV and syphilis infections were significantly higher among women who aged 40 years or older, worked in small commercial sex venues or on street, divorced or widowed, or no formal schooling. A very high HIV infection prevalence (8.2%) was observed among a small number of cross-border foreign FSW (n=49). The prevalence of HCV infection did not differ by most of the demographic characteristics. Living in other provinces or being a Zhuang-ethnic served as protective factors for HCV. The multivariable analyses confirmed the results of bivariate results suggesting higher prevalence of HIV and syphilis infections among FSW who were older, divorced or widowed, or no formal schooling. Future HIV intervention prevention efforts among FSW need to pay particular attention to these women in order to effectively curtail the infections among this most-at-risk population as well as to prevent the further spread of HIV and syphilis to other populations.