Objective: To understand the relationship between childhood abuse and uncertainty stress among college students and their interaction with depressive symptoms, so as to provide evidence for psychological intervention among college students. Methods: A total of 1 830 college students from Xuzhou, Nanjing and Wuhan were selected by multistage stratified cluster random sampling method to conduct a questionnaire survey from March to May 2021 using Adverse Childhood Experience Scale, Uncertainty Stress Scale, and 10-Item Center for Epidemiological Studies Depression Scale. Results: Overall, 361 (19.73%), 507 (27.70%) and 607 (33.17%) college students had childhood abuse experiences, high uncertainty stress and depressive symptoms respectively. After controlling for confounding factors, multivariate Logistic regression analysis showed that the risk of depressive symptoms in college students with childhood abuse experiences was 2.84 times higher than those without childhood abuse experiences ( OR= 2.84 , 95%CI =2.17-3.71). The risk of depressive symptoms among college students with high uncertainty stress was 7.88 times higher than those without high uncertainty stress ( OR=7.88, 95%CI =6.21-9.99). The results of interaction analysis showed that childhood abuse and uncertainty stress had no multiplication interaction but additive interaction on depressive symptoms of college students: RERI (95% CI )=12.73(3.24-22.23), AP (95% CI )=0.57(0.37-0.76), S (95% CI )=2.47(1.53-3.98). Conclusion High uncertainty stress and childhood abuse have additive interaction on depression symptoms of college students. Eliminating childhood abuse and scientific management of uncertainty stress can reduce the risk of depressive symptoms among college students.