Background: Depression is a mental illness that disturbs an individual’s health, which exacerbates the development of BC and reduces the quality of an individual’s life. Objective: To investigate the impacts of Traditional Chinese Medicine Music (TCMM) intervention on the depressed BC mouse model and explore the potential underlying mechanisms. Methodology: The intervention of TCMM and its impact on the body weight, tumor size, tumor weight, and behavioral tests were conducted in Chronic Mild Stress (CMS) induced MMTV-PyMT mice. Furthermore, CMSinduced oxidative stress-related Thioredoxin-1 (TRX-1) was also determined using western blot. A clinical trial was conducted to validate the effect of stress-related TRX-1 during the intervention of TCMM. Results: The outcome of the study showed that mice under the environment of TCMM significantly reduced the breast tumor size, tumor weight, and behavioral changes. TRX-1 was significantly increased in the CMS-induced BC mice which were attenuated by the intervention of TCMM. More interestingly, plasma TRX-1 was also significantly reduced using the intervention of TCMM in BC patients. Conclusion: Based on the experimental and clinical findings, we strongly suggest that TCMM therapy could decrease CMS-induced tumor development in the breast and improves the quality of life in depressed BC individuals. Furthermore, the relationship between TRX-1 and TCMM has to be investigated, which is now underway.