Background Breast cancer remains the most important cancer among women worldwide. The disease itself and treatment may have a profound impact on the patients' psychological well being and quality of life. Depression is common in breast cancer patients and affects the therapeutic effects as well as prolongs the duration of hospital stay. However,few studies reported the effectiveness of music therapy on depression and duration of hospital stay of female patients with breast cancer after radical mastectomy. Methods One hundred and twenty subjects were recruited to this clinical trial and randomly allocated to two groups.The experimental group (n=60) received music therapy on the basis of routine nursing care, whereas the control group (n=60) only received the routine nursing care. The whole intervention time was from the first day after radical mastectomy to the third time of admission to hospital for chemotherapy. Data of demographic characteristics and depression were collected by using the General Questionnaire and Chinese version of Zung Self-rating Depression Scale (ZSDS)respectively. One pre-test (the day before radical mastectomy) and three post-tests (the day before discharge from hospital, the second and third admission to hospital for chemotherapy) were utilized. Duration of hospital stay was calculated from the first day after radical mastectomy to the day of discharged from hospital. Results The mean depression score of all subjects was 37.19±6.30. Thirty-six cases (30%) suffered from depression symptoms, with 26 (72.2%) mild depression cases, 9 (25.0%) moderate depression cases, and 1 (2.8%) severe depression case. After music therapy, depression scores of the experimental group were lower than that of the control group in the three post-tests, with significant differences (F=39.13, P