Objectives: The violence and prostitution are examples of the stressors in the women with high-risk sexual behaviors and can create a psychological crisis in these women. The purpose of this study was to determine the relationship of mental health with social support in the women with high -risk sexual behaviors visiting drop-in centers (DICs) in Tabriz, Iran, in 2017. Materials and Methods: This cross-sectional study was conducted on 149 women with high-risk sexual behaviors, visiting three DICs in Tabriz, Iran. The sampling was purposive and non-random. Data were collected using socio-demographic characteristics, social support (PRQ-part 85), and mental health (GHQ-28) questionnaires. A test of multivariate linear regression was performed to identify a number of mental health determinants and explanation of variance. Results: The mental health score was 50.7 (18.2), the score ranged from 0-84. The best status belonged to depression subscale [10.5 (7.1)] and the worst status belonged to social dysfunction subscale [14.6 (4.5)]. The mental health and its subscales had a significant relationship with social support (P<0.001, R= -0.55 to -0.33). The variables of social support, drug use, and spousal violence were able to predict 35.4% of mental health variance in the women. Conclusions: According to the results, appropriate strategies are needed to promote social protection and mental health in the women with high-risk sexual behaviors in order to reduce the sexually transmitted diseases especially HIV/AIDS in the society.