BACKGROUND The COVID-19 outbreak has gradually become more normal. College students, one of the groups most affected by the epidemic, often suffer from varying degrees of psychological problems. The prevention and improvement of college students' psychological problems are particularly important for both individuals and society. OBJECTIVE The purpose of this study was to explore (1) the changes in college students’ negative emotions during the epidemic containment period, (2) the correlation between negative emotions and healthy behaviors, and (3) the main factors that can affect negative emotions in healthy behaviors. METHODS A total of 5872 Chinese college students was selected as subjects in this study. The negative emotion Scale (DASS-21) and the health Behavior Scale (HPLP-Ⅱ) were used to investigate the level of negative emotions and health behaviors on November 12, 2021, and June 17, 2022, respectively. RESULTS The results obtained in this study have shown the significant differences between negative emotions and health behavior scores at two-time points. And there was a negative correlation between negative emotions and health behaviors. The former negative emotions can predict later health behaviors, and the former health behaviors can predict later negative emotions. In addition, stress management, spiritual growth, and responsibility for health in health behaviors have a strong correlation with negative emotions, which are the main influencing factors to reduce negative emotions in college students. CONCLUSIONS The results of this study suggest that the psychological problems of college students have become particularly serious under the dual influence of campus lockdown and academic pressure during the epidemic. Positive health behaviors may be beneficial to reduce the negative emotions of college students. Therefore, we should pay more attention to their mental health problems by reminding and guiding them to adopt a healthy lifestyle, to prevent and improve the mental health problems that they may have been accumulating, and for supporting them when necessary.