Objective To explore the mediating effect of social support on the relationship between negative emotion and coping style in human immunodeficiency virus (HIV)-infected pregnant women. Methods A total of 202 HIV-infected pregnant women were enrolled by a convenient sampling method in this study. Participants completed questionnaires including social support rating scale (SSRS), knowledge, attitudes and practices scale for preventing mother-to-child transmission of human immunodeficiency virus (KAPS-PMTCT), self-rating anxiety scale (SAS), self-rating depression scale (SDS), Berger HIV stigma scale (BHSS), and simplified coping style questionnaire (SCSQ). The relationships of these variables were analyzed by Pearson correlation analysis and structure equation modeling analysis. Results The correlations between negative emotion, social support and coping style were all significant. Social support was negatively correlated with negative emotion (P<0.05) and negative coping style (P<0.01), and was positively correlated with positive coping style (P<0.01). Negative emotion was weakly negatively correlated with positive coping style (P=0.07), and was strongly positively correlated with negative coping style (P<0.01). Structure equation modeling analysis showed that negative emotion indirectly affected the coping style of HIV-infected pregnant women mainly through the mediating effect of social support (χ²/df=1.835, foodness of fit index[GFI]=0.975, adjusted goodness of fit index[AGFI]=0.961, normed fit index[NFI]=0.950, incremental fit index[IFI]=0.938, comparative fit index[CFI]=0.981, parsimony comparative fit index[PCFI]=0.452, root mean square error approximation[RMSEA]=0.064), with the total amount of mediating effect of the positive coping style and negative coping style being -0.273 and 0.522, respectively. Conclusion Social support is an important mediator between negative emotion and coping style in HIV-infected pregnant women.