Objective <p>To evaluate the effects of relaxation training combined with music-based intervention on anxiety and depression in patients undergoing hematopoietic stem cell transplantation (HSCT).</p> Method <p>This quasi-experimental study included patients with hematologic tumors who underwent HSCT at the Affiliated Hospital of Xuzhou Medical University between July 2022 and November 2023. Participants were divided into a control group and an experimental group. The control group received conventional care, while the experimental group received relaxation training combined with music-based intervention in addition to conventional care. A total of 62 patients completed the study. Anxiety and depression levels were assessed using the 7-item Generalized Anxiety Disorder Scale (GAD-7) and the 9-item Patient Health Questionnaire (PHQ-9), respectively. Biological indicators related to anxiety and depression, including blood pressure, heart rate, and cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), were also evaluated.</p> Results <p>Compared with the control group, the experimental group demonstrated significant reductions in depression, blood pressure, and cytokine levels of IL-1β, IL-6, and TNF-α. However, no statistically significant changes were observed in anxiety or heart rate.</p> Conclusion <p>Relaxation training combined with music-based intervention effectively alleviated depression in HSCT patients and influenced biological markers associated with anxiety and depression, including blood pressure and cytokines IL-1β, IL-6, and TNF-α. Nonetheless, no significant changes was noted in anxiety or heart rate.</p> Trial and protocol registration <p>This study has been registered on the International Traditional Medicine Clinical Trial Registry, with the clinical trial registration number ITMCTR2025000412.</p>