Introduction: Depression is considered as a disorder that students have a susceptible environment for it and is affected by many factors. Therefore, the purpose of this study was to determine the role of satisfaction of basic psychological needs and family functioning by interdisciplinary role of emotion regulation difficulty in the prediction of depression. Methods: The method used in the study is descriptive approach by structural equation modeling. The sample consisted of 452 (207 boys and 245 girls) students universities Tabriz who were selected using multistage cluster sampling. Then, they filled out depression Questionnaire, satisfaction of basic psychological needs, family Assessment Device and Difficulties in Emotional Regulation Scale. Data were analyzed by using Pearson correlation coefficient, cronbach alpha and structural equation modeling. Results: The results of the study showed that the goodness of fit index (GFI), adjusted goodness of fit index (AGFI), comparative fit index (CFI), is greater than 0.90 and root mean square error of approximation (RMSEA), and root mean square residual (RMR) index is less than 0.05. Therefore, the proposed model has had a very suitable fitness with data. In this study, the most direct effect is the satisfaction of basic psychological needs on depression with a coefficient of-0.38 and satisfaction of basic psychological needs has the most indirect effect through emotion regulation difficulty on depression with a coefficient of-0.12. Conclusion: Based on the results of the present study, it can be concluded that Difficulties in Emotional Regulation As a Mediator of the Relationship between satisfaction of basic psychological needs and family function can explain depression in College Students and, thereby, attention to this matter can lead to the proposal of some recommendations for depression in College Students prevention and treatment.