Depression has been associated with numerous adverse health conditions. This study sought to determine the frequency of significant depressive symptoms and whether or not acculturative stress, discrimination, and reproductive health conditions were risk factors for significant depressive symptoms in migrant working women in China. The design of this study is cross-sectional. Data were derived from a survey of female migrant workers at three employment sites in Changsha, China. The associations between acculturative stress, discrimination, reproductive health, and risk for significant depressive symptoms were obtained using F-tests for mean differences, correlations, ordinary least squares regression, and logistic regression analysis. Between March and June 2017, 232 eligible female participants completed the survey among whom the median age was 34.36 years (standard error 0.43) and 25.58% reported significant depressive symptoms. Significant depressive symptoms were associated with higher education (F-test, P =.006), all four acculturative stress factors (r = 0.15 to r = 0.29), both institutional and interpersonal discrimination (r = 0.29, r = 0.35), age (r = − 0.13), and self-rated health (r = − 0.19). In multivariate regression analysis of depression scale scores, interpersonal discrimination was the strongest predictor (beta = 0.238, P =.002) among the nine factors identified in bivariate analysis. None of the other predictors (age, self-rated health, education, acculturative stress, and institutional discrimination) showed significant associations with the depression scale. Similar results were obtained for a multivariate logistic regression analysis of a clinically important threshold for depression (<10 versus ≥ 10 on the depression scale). Only interpersonal discrimination significantly distinguished between clinical depression categories (odds ratio = 2.607 per unit change in the index, P =.001). Migrant women workers in China appear to be at risk for significant depressive symptoms, and interpersonal discrimination appears to be an important risk factor in this setting. Acculturative stress and institutional discrimination may also be relevant risk factors, as suggested in our bivariate analysis, but in our sample, the correlations between the stress and discrimination factors are high enough to compromise identification of unique associations between acculturation stress and depression. Government, community and workplace education, and psychosocial services for migrant women are recommended. • Twenty five percent of female migrant workers in China could be regarded as mentally unhealthy. • More education and acculturative and discrimination stress are associated with depressive symptoms. • Increasing age and poor self-rated health are associated with depressive symptoms. • Interpersonal discrimination is predictive of significant depressive symptoms. [ABSTRACT FROM AUTHOR]