Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, painful, and debilitating side effect of many standard chemotherapy regimens. CIPN symptoms include pain, paresthesia, and muscle weakness, and patients may exhibit functional decline and lower quality of life. Our prior study showed more than half of breast cancer survivors experience persistent CIPN up to a mean duration of 5.6 years, which is associated with a doubled fall risk. Identifying non-pharmacological approaches to reduce CIPN symptoms and improve cancer survivors’ outcomes is urgently needed. Yoga is a meditative movement therapy that includes stretching, and flexibility and balance training. Our pilot study (NCT03292328) demonstrated that yoga reduced CIPN-related symptoms, and improved quality of life and functional reach scores compared to waitlist control. We hypothesize that yoga can reduce CIPN symptoms, improve function, and reduce the risk of falls. Methods: We are conducting a three-arm randomized education and usual care-controlled trial in cancer survivors with chronic CIPN pain at Memorial Sloan Kettering Cancer Center (MSK), New York, NY. Participants in the intervention arm will receive twice-weekly one-hour Hatha yoga classes taught virtually by MSK instructors and practice yoga at home daily for eight weeks. Participants in the education control arm will receive one-hour virtual education classes twice per week taught by an MSK instructor for eight weeks. Participants in the usual care arm will continue their usual care for CIPN for eight weeks. The primary endpoint is the Brief Pain Inventory-Short Form average pain item at weeks 8 and 24. Secondary outcomes include the Neuropathic Pain Scale, Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity, Patient-Reported Outcomes Measurement Information System Global Health, Brief Fatigue Inventory, Insomnia Severity Index, Hospital Anxiety and Depression Scale, Quality of Life Questionnaire of CIPN twenty-item scale, functional assessments, and quantitative sensory testing at weeks 0, 4, 8, 12, 18, and 24. Eligibility criteria include: 1) Moderate-to-severe CIPN pain, defined by a score of 4 or greater on a 0-10 numerical rating scale; 2) completion of neurotoxic chemotherapy at least three months prior; 3) no changes in anti-neuropathy medications within three months of enrollment; and 4) changes in balance and functionality. As of February 2023, we have accrued 64 of our total target of 268 participants. We anticipate completing accrual in March 2025. We have 35 participants in the yoga intervention, 15 participants in education control, and 14 participants in usual care control. The majority (89%) of participants are female and 11% are male. 78% of our participants are white, 16% are black or African American, 1% are Asian, and 5% identify as more than one race. Clinical trial information: NCT05121558.