The purpose of this study was to investigate the relationship between stress and depression by using coping style as a mediator among clinical nurses in Taiwan. The results of this study indicated that stress is strongly associated with depression, and coping style plays an effective mediator in reducing depressive symptoms. Therefore, strategies in reducing depressive symptoms should be an important agenda for nursing education. Relevant healthcare and nursing managers and administrators should pay immediate attention to this issue to enhance medical service quality and provide proactive strategies for nursing education.