BACKGROUND : Cyberbullying is a serious social issue that can cause a number of psychological and behavioral problems for perpetrators and victims. Previous studies have shown that adolescent victims of cyberbullying are more likely to exhibit depressive symptoms. However, few studies have investigated the relationship between the perpetration of cyberbullying and depression, or the mediating and moderating mechanisms underlying this relationship. METHODS : A questionnaire survey was conducted among 476 college students to investigate the relationships between cyberbullying perpetration and depression, the mediating role of social anxiety, and the moderating role of neuroticism. RESULTS : The results showed that cyberbullying perpetration had a significant and positive predictive effect on depression. Social anxiety partially mediated this relationship. The direct predictive effect of cyberbullying perpetration on depression, and the relation between social anxiety and depression, were both moderated by neuroticism. Cyberbullying perpetration had a greater impact on depression for college students with lower levels of neuroticism and the predictive function of social anxiety on depression was stronger for individuals with low levels of neuroticism too. But neuroticism did not moderate the association between cyberbullying perpetration and social anxiety. CONCLUSIONS : This study focused only on the individual variables influencing the relationship between cyberbullying perpetration and depression, and did not examine interpersonal or environmental variables. Also, the cross-sectional research design means that causality cannot be deduced from the results. CONCLUSIONS : Cyberbullying perpetration can predict depression directly, and also indirectly via the mediating role of social anxiety. Neuroticism moderates the relation both between cyberbullying and depression, and between social anxiety and depression. These findings provide new perspectives for the treatment and prevention of depression among college students.