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Objective: This study aimed to understand the herpes simplex virus-2 (HSV-2) infection and related factors among female drug abusers in the women's compulsory drug rehabilitation center of Shandong province and to provide reference for the prevention and control of HSV-2 in these settings. Methods: We screened all of 451 female drug abusers in the women's compulsory drug rehabilitation centers in of Shandong province and conducted a study using both questionnaire investigation and serological tests for HSV-2, HIV and syphilis. We also used EpiData 3.1 software to establish a database and SPSS 20.0 software to conduct the χ (2) test and multivariate logistic regression analysis. Results: A total of 451 female drug abusers were under study. We noticed that the rates for HSV-2 infection, HIV infection and syphilis infection appeared as 72.1% (325/451), 2.2% (10/451) and 33.5% (151/451) respectively. Results from univariate analysis showed that factors as: awareness on AIDS, having temporary sex partner after using the drug, having multiple sex partners after using the drug, providing commercial services or having temporary sex practice before being detained, with syphilis infection etc ., were associated with HSV-2 infection. Data from the multivariate analysis showed that the OR (95% CI ) value of HSV-2 infection was 2.90 (1.19-7.06) for those who providing commercial service, when comparing to those who did not. Compared to those who did not suffer from syphilis infection, the OR (95% CI ) value of HSV-2 infection for those with syphilis infection was 2.75 (1.63-4.63). Conclusions: The rate of HSV-2 infection was high in the women's compulsory drug rehabilitation center of Shandong province. We should enhance measures and promote condom use to prevent from HSV-2 and other sexually transmitted diseases among them.