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BACKGROUND A mindfulness-based stress reduction program combined with music therapy is one of the interventions designed to help patients cope with stress and depression. OBJECTIVE The aim of this study was to examine the effects of an online mindfulness-based stress reduction program combined with music therapy on stress, depression, and psychological well-being in adult patients with cancer. METHODS This study was a single-blinded, prospective, randomized-controlled experimental design. One hundred twenty cancer patients were recruited (60 each in the intervention and control groups). Patients in the intervention group received a 10-day mindfulness-based stress reduction program combined with music therapy. Stress was measured with the State Trait Anxiety Inventory-State, psychological well-being was measured with the Psychological Well-being Scale, and depression was measured with the Beck Depression Inventory at baseline and the end of the study. RESULTS The intervention group showed significantly lower stress and depression scores than the control group in the total scores at 10 days (P < .05). The intervention group had significantly higher scores in the psychological well-being (P < .001) than the control group at 10 days. Intragroup comparison of the stress and depression scores showed that posttest score of the intervention group was significantly lower than its pretest score (P < .05). CONCLUSION Mindfulness-based stress reduction program combined with music therapy reduced the levels of stress and depressive symptoms and improved psychological well-being in cancer patients. IMPLICATIONS FOR PRACTICE A nurse-led mindfulness-based stress reduction program combined with music therapy is an innovative and effective psychological intervention that may be integrated with regular patient care for adults receiving treatment of cancer.