Objective　This study is to explore the association between self-differentiation and men-tal health among medical students. Methods　Differentiation of self inventory-revised (DSI-R) and univer-sity personality inventory (UPI) were used to measure the self-differentiation and mental health of 526 med-ical students from Grade One to Grade Five at a comprehensive university in Shanghai. Result　The mean score of DSI-R was (171.25±19.65). 32.2% of participants had different levels of mental health prob-lems. Female students got higher score of DSI-R than male students (P=0.007). Statistically significant dif-ferences of medical students' self-differentiation were found among years of school attended (P=0.039). Sta-tistically significant differences of self-differentiation were also found between the first class and the third class of UPI (P<0.001) as well as the second class and the third class of UPI (P=0.004). Ordinal regression analysis indicated that self-differentiation was a risk factor for medical students' mental health (OR=1.036

P=0.000). Conclusion　The average score of medical students' self-differentiation was higher than college students of other specialties. But their mental health condition was worse. Medical students with higher self-differentia-tion had worse mental health situation.