Objective: To investigate the association between the family relationship of college students in Shanghai and the psychological stress response under the COVID-19 epidemic. Methods: Totally 904 college students from universities in Shanghai were investigated with questionnaire of FACESII-CV and IES-R. Results: The score of family relationship intimacy was(61.32±6.29), the score of family relationship adaptability was(43.30±5.83), the score of psychological stress was(30.77±7.33), the score of internal dimension，avoidance, high alertness were(11.63±2.53)(11.69±2.64)(7.45±2.33). About 77.5%(701) and 17.3%(156) of college students showed mild and moderate stress reactions. Three dimensional scores of psychological stress response and two dimensional scores of family relationship differed significantly by age, grade, family income and parental education(P<0.01). Moreover, family relationship intimacy and adaptability scores showed negative associations with intrusive symptoms, avoidance symptoms, and high alert symptom dimension scores(P<0.05). Conclusion College students showed mild psychological stress under the COVID 19 epidemic with intrusion and avoidance symptoms as the most common. The intimacy and adaptability of family relationships are negatively associated with psychological stress response of college students under the epidemic. High-quality family relationships can reduce the psychological impact and adverse effects of the new crown epidemic on college students.