Objective: To investigate the effects of major family structure changes on depression, anxiety and stress symptoms of college students, and to provide theoretical basis for mental health promotion and prevention. Methods: A questionnaire survey was conducted among 9 779 college students from 6 universities, including Jiangxi University of Finance and Economics, Shangrao Normal University, Gannan Normal University, Fujian Polytechnic Normal University, and Changjiang University, by using the Depression, Anxiety and Stress Scale 21 Items (DASS 21). Results: The prevalence rates of depression, anxiety and stress symptoms among college students were 27.4%, 42.0% and 17.4%, respectively. Univariate analysis showed that family structure was associated with anxiety and stress symptoms ( χ 2=8.40,13.08, P <0.05). Multivariate Logistic regression analysis showed that specific family structure other than single or two parent family was positively correlated with anxiety( OR =1.89,95% CI =1.05- 3.42 ) and stress symptoms ( OR =2.48, 95% CI =1.36-4.50), family structure changes due to parental divorce was positively correlated with stress symptoms ( OR =1.53,95% CI =1.05-2.20)( P <0.05). Conclusion The occurrence of depression, anxiety and stress symptoms of college students is related to the type of family structure and the changing factors. Colleges should pay more attention to the mental condition of college students with family structure changes, and deliver various mental health promotion services including psychological counseling and health education.