Background: Numerous studies have demonstrated that spirituality has protective effects on depression. However, there are only few studies on the theoretical mechanism showing how spirituality effects on depression. Thus, to find mediating variables explaining the relationship between the spirituality and depression may help to develop appropriate program for reducing depression in elderly cancer patients. In this study, we examined the effect of optimism and pessimism as their mediating effects on depression. Methods: This study is to verify the relationships between spirituality and depression along with the mediating effects of optimism and pessimism among 600 South Korean elderly cancer patients who participated in a community-based study about their mental health. Results: Optimism and pessimism are linked with spirituality and depression. Higher spirituality levels were associated with increased optimistic thinking, and then optimistic thinking is associated with low possibility of depression, whereas lower spirituality levels were associated with more pessimistic thinking, and in turn pessimistic thinking is associated with high depression scores. Conclusions: Understanding optimism and pessimism affecting depression level is critical for developing spirituality-based programs to reduce depression in elderly cancer patients. Korean J Health Promot 2016;16(2):127-133