Background: Social change, intensified by industrialization and globalization, has not only changed people's work lives but also their personal lives, especially in developing countries. The aim of this study was to provide evidence and recommendations regarding family structure, function, and mental health to actively respond to rapid social change. Methods: A cross-sectional survey was conducted face-to-face and door-to-door from July 2011 to September 2012 in Hubei Province, central China. Family structure comprised alone, couple, nuclear family, and extended family; family function was measured using the family APGAR (Adaptation, Partnership, Growth, Affection, and Resolve) scale, and mental health was measured using the Chinese version of the 12-item General Health Questionnaire (GHQ-12). Results: The urban-vs-rural difference of family structure among alone, couple, nuclear family, and extended family was statistically significant (5.21% vs 4.62%; 27.36% vs 13.14%; 33.22% vs 27.74%; 34.20% vs 54.50%, respectively; p < 0.0001); and those difference of family function was not statistically significant (8.11 +/- 2.13 vs 8.09 +/- 2.27, p = 0.9372). The general linear regression showed that the effect of family structure on mental health, whether urban or rural, was not significant, however, the effect of family function was significant, especially regarding better family functioning with better mental health. Conclusions: Combined the effects of family structure and function on mental health, the external form of family (family structure) may not be important; while the internal quality of role (family function) might be key. Improving the residents' family function would be a priority strategy for family practice with their mental health.