Objective To explore the effects of live music to decrease psychological distress in adolescent and young adult (AYA) patients undergoing hematopoietic stem cell transplantation (HSCT). Method A quasi-experimental study was conducted. Sixty patients undergoing HSCT were divided into two groups, receiving either 4 week of live music (n = 31) or standard care (n = 29). Psychological distress, anxiety, the severity of symptom clusters and symptom interference were measured. Results When compared with the immediately and 1 month after intervention, patients in LM intervention group had significantly lower psychological distress and anxiety level than wait-list group. AYA undergoing HSCT reported significantly milder general symptom cluster and neurological symptom cluster at T3 than at baseline. Conclusions Live music intervention showed a positive effect on relieving psychological distress and anxiety in AYA patients undergoing HSCT. However, further researches are warranted to explore the effects of live music intervention on symptom cluster.