Physical inactivity is the fourth leading risk factor for mortality globally and causes 6% of all deaths worldwide. This study explored the relationships among physical activity, self-efficacy, and quality of life and tested whether self-efficacy mediates the effect of physical activity on quality of life in patients with cancer. A cross-sectional design was adopted, and 150 patients with cancer who had undergone radiotherapy were recruited. Instruments included the Godin Leisure-Time Exercise Questionnaire physical activity preference survey form, European Organization for Research and Treatment of Cancer QLQ-C30, and physical activity self-efficacy scale. Of the patients in this study, 24% matched the suggestion for physical activity. The self-efficacy score was low (mean= 2.33±1.37). The quality of life score was average (mean= 45.72±17.21). Physical activity was positively related to self-efficacy. Physical activity and self-efficacy were positively interrelated to quality of life in the patients (r=0.336-0.549, p＜ .001). Self-efficacy completely mediated the effects of physical activity on quality of life. These tests were conducted to explore how the phenomenon of self-efficacy affects quality of life in patients with cancer and to investigate the mediating role of self-efficacy in the effects of physical activity on quality of life. The current findings are of clinical importance and can serve as a reference for how to improve the effect of self-efficacy on physical activity among patients with cancer.