Objective To analyze the psychological and behavioral status and influencing factors of college students during the epidemic of COVID-19 in Wuhan. Methods The students from two universities in Wuhan area were selected by stratified cluster sampling, and the self-designed questionnaires were used to conduct the online survey. Statistical analysis was performed using SPSS 22.0. Results Among 3 966 college students surveyed in this study, the proportion of students in Wuhan who thought that their own infection probability was higher than others (11.25%), that their family members were more likely to be infected (15.29%), that they were very worried about their own infection (22.93%), that they were very worried about the infections in the same community (25.27%), and that their own infection risk was higher than others (9.77%), was higher than those of students in other three regions. The total incidence of depression was 27.10%. Multivariate logistic regression analysis showed that the humanities and social science majors living in the city, worrying about the infection of themselves and their families, feeling that they had a higher chance of infection than other, being not optimistic about the epidemic situation, and thinking that the infection had a great impact on people's emotions were the risk factors of depression during the epidemic. Conclusion College students in Wuhan had psychological and behavioral problems during the COVID-19 epidemic. These problems were related to whether they were located in the epidemic area and whether they were worried about infections.