Objective: To explore the relationship between eHealth literacy and social support and depressive symptoms in female nursing students, and to provide a reference for improving the mental health of female nursing students. Methods: In November 2019, 1 115 female nursing students from freshmen to junior years in four medical colleges in Changsha were investigated eHealth Literacy Scale, Perceived Social Support Scale, Center for Epidemiological Studies Depression Scales and demographic information questionnaire. Results: The detection rate of depressive symptoms in female nursing students was 20.1%(224/1 115), and the qualification rate of eHealth literacy was 29.2%(326/1 115). The incidence of depressive symptoms were higher in female nursing students with urban household registration and their parents with high school education and above and poor family economic status(χ2=9.46, 20.02, 7.16, 12.40, P<0.05). Multivariate Logistic regression analysis showed that poor eHealth literacy and low social support were positively correlated with depressive symptoms in female nursing students(OR=3.16, 3.65, P<0.05). There was a correlation between the interaction of eHealth literacy and social support with depressive symptoms. In the same type of social support, the lower eHealth literacy level, the greater the risk of depressive symptoms was for female nursing students(P<0.05). Conclusion Health literacy and social support are the influencing factors of depressive symptoms in female nursing students. The occurrence of depressive symptoms can be reduced by improving the level of electronic health literacy and social support.