BACKGROUND: with the increase of study and life pressure, the number of depressed college students showed an increasing trend year by year, and the drug treatment alone could not achieve a comprehensive recovery of depression patients, so it was more necessary to pay attention to the spiritual treatment. OBJECTIVE: this research aimed to better understand the relationship between college students’ depression and life events, social support, psychological pressure, and coping style, and the influence of systematic family therapy on depression degree, psychological stress, and social adaptability of college students with depression. METHODS: in this study, 105 college students with depression were selected as the research object, and healthy college students were taken as the control group. Through questionnaire, the differences in life events, social support, psychological stress, and coping styles between the groups were compared. The correlation between the degree of depression and various variables were analyzed, and the impact path of each variable on depression was analyzed using the path analysis model. Depression patients were then divided into a conventional group treating with conventional medications and an observation group treating with systematic family interventions. Differences in Hamilton Depression Scale-17, (HAMD-17), CPSS, and Social Adaptive Functioning Evaluation (SAFE) scores were compared and analyzed between the two groups before treatment (T1), during the treatment (T2), and after treatment(T3). RESULTS: there were significant differences in scores of life events, social support, psychological stress, and coping styles between the healthy control group and the depressed patients (P < 0.05). There was an obvious correlation between different depression degrees and life events, social support, psychological stress, and coping styles (P < 0.05). Life events, social support, and psychological stress had a direct and significant impact on depression (0.250, 0.218, and 0.392; P < 0.05), and they also had an indirect and significant impact on depression through coping styles (P < 0.05). The systematic family treatment model could significantly reduce HAMD-17 and CPSS scores (P < 0.05), and significantly improve SAFE scores (P < 0.05). CONCLUSIONS: adverse life events, lack of social support, excessive psychological stress, and negative coping styles can aggravate college students’ depression. Systematic family therapy can improve the degree of depression, reduce the psychological stress, and enhance the social adaptability of college students with depression.