Although defending self-efficacy is related to defending behavior in cyberbullying, little is known about the underlying mechanisms of this association. This study explored the relationship between defending self-efficacy and defending behavior. In a China sample, it examined the mediating role of defending intention and the moderating role of empathy in the association between defending self-efficacy and defending behavior. A cross-sectional sample of 672 Chinese adolescents (Mage = 14.86, SD = 1.74) completed a questionnaire, which includes measures of defending self-efficacy, defending intention, empathy, and defending behavior. Results showed that defending self-efficacy was significantly and positively associated with defending behavior. Mediation modeling indicated that defending self-efficacy directly affected defending behavior and could indirectly affect defending behavior through the mediating role of defending intention. In addition, the mediation role of defending intention was moderated by empathy, and as the level of empathy increased, the effect of defending self-efficacy on defending intention became stronger, and the effect of defending intention on defending behavior became stronger. These findings advance our understanding of how and when defending self-efficacy is related to defending behavior in cyberbullying among adolescents. It also sheds some light on preventing and intervening in adolescent cyberbullying from a bystander’s perspective.