Our objective was to estimate, at the general population level, the variance in prevalence of depression attributable to family environment. A cross-sectional survey was conducted door-to-door in rural China with a sample of 3720 individuals aged 18 years and older. Results showed that the difference in depression prevalence between extended and nuclear families was not statistically significant. In addition, the association of family structure and depression (for males and females) was not statistically significant after adjusting for potential confounding variables. The association of family-related negative life events and economic status of the family with depression (for males and females) was statistically significant. The association of family support and depression was statistically significant for males but not for females. Findings suggest that the Chinese traditional extended family may not be protective against depression at the general population level, and family interventions targeting family environment should reflect the above gender differences.