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Abstract Background Women having multiple sex partners are reportedly at an increased risk of HPV infection. However, the prevalence and risk factors of HPV infection in female sex workers (FSWs) vary considerably across racial/ethnic, socioeconomic, and geographic groups. This study aimed to determine the prevalence and risk factors of HPV infection in FSWs in Northeast China. Methods A total of 309 FSWs identified and approached through a local police office and 1000 healthy subjects from a single factor undergoing annual gynecological examinations in Shenyang were recruited. A liquid-based ThinPrep Pap test and the Hybrid Capture II-based high-risk HPV DNA test, with or without a colposcopic examination, were performed on both FSWs and control subjects. Data on HPV infection and histological and cytological lesions of the cervix were obtained and analyzed. A questionnaire survey was administered to all 309 FSWs with their socio-demographic and behavioral information collected. The association of various socio-demographic and behavioral variables with HPV infection was assessed. Results HPV was significantly more prevalent in FSWs (61.90 %) than in healthy control subjects (21.00 %) ( P < 0.01), so were cervical lesions ( P < 0.01). HPV prevalence in our sample of FSWs fell in the upper range of reported values in FSWs across different countries, and was similar to that for FSWs in the southeast Chinese city of Huzhou but higher than that for FSWs in southwest China, Guangxi, as compared with data from other studies within China. HPV infection in FSWs was significantly associated with the age at first sexual intercourse (OR 0.699, 95 % CI 0.492–0.992) and post-menopause (OR 2.928, 95 % CI 1.099–7.800) ( P < 0.05). Conclusions FSWs are at a substantially high risk of HPV infection and cervical dysplasia development as compared with healthy control subjects in Shenyang, China. Age of first sexual intercourse and post-menopause are two independent risk factors for HPV infection in this special group of population. Intensified and coordinated efforts from government, public health sector, communities and families are needed to reduce the risk of HPV infection in this specific group of population.