Evidence has shown that survivors of pediatric brain tumors have more negative psychological sequela, particularly depression, than do survivors of other childhood cancers. This study examined the efficacy of a musical training program in reducing depressive symptoms and enhancing self-esteem and quality of life in Hong Kong Chinese pediatric brain tumor survivors. A prospective randomized controlled trial, two-group pretest and repeated posttest, between-subjects design was conducted to 60 pediatric brain tumor survivors (8-5years old). Participants in the experimental group received a weekly 45-min lesson on musical training for 52weeks. Participants in the control group received a placebo intervention. The primary outcome was depressive symptoms at 12months. Secondary outcomes were self-esteem and quality of life at 12months. Data were collected at baseline and 6 and 12months after the intervention began. Participants in the experimental group reported statistically significant fewer depressive symptoms (P<0.001), higher levels of self-esteem (P<0.001), and better quality of life (P<0.001) than the control group at 12-month follow-up. This study provides evidence that musical training is effective in reducing depressive symptoms and enhancing self-esteem and quality of life in Hong Kong Chinese pediatric brain tumor survivors. These results indicate that musical training is not only a leisure activity but also carries therapeutic effects in promoting psychological well-being and quality of life in pediatric brain tumor survivors.