CONTEXT: Adolescent and young adults (AYAs) with cancer experience significant psychological distress due to cancer treatment that can persist long after treatment. However, little is known regarding optimal interventions to support the psychosocial needs of AYAs with cancer. OBJECTIVE: The overall objective of this single arm, longitudinal, pilot study was to determine the feasibility of implementing a mindfulness-based music therapy intervention to improve anxiety and stress in AYAs receiving cancer treatment. METHODS: AYAs (15 - 39 years old) who were to receive cancer treatment for ≥ eight weeks were recruited from the pediatric, melanoma, sarcoma, breast, lymphoma, and leukemia oncology outpatient centers at Dana-Farber Cancer Institute. The music therapy intervention included four sessions of individual mindfulness-based music therapy in-person or using Zoom over twelve weeks. Prior to-and after the intervention period, participants completed the Patient-Reported Outcomes Measurement Information Anxiety 4a and Perceived Stress Scale. Changes in patient-reported outcomes are compared using Wilcoxon signed-rank tests. RESULTS: Over ∼14 months, 37 of 93 eligible AYAs were enrolled to the study (39.8% consent rate). Overall, 27 of 37 (73%) participants (Median age=32; 56.8% Female) completed at least two music therapy sessions and the baseline measures and end of study measures. Participation in the mindfulness-based music therapy sessions resulted in significant pre-to-posttest improvements in perceived stress (median change: -4.0, P = 0.013) and non-significant changes in anxiety (median change: -1.9, P = 0.20). Satisfaction and acceptability were highly rated. CONCLUSIONS: The delivery of a four-session mindfulness-based music therapy intervention to AYAs receiving chemotherapy was feasible and significantly improved perceived stress. These preliminary findings should be confirmed in a randomized controlled trial. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03709225.