Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect in cancer survivors that can last long after completion of neurotoxic chemotherapy. Patients with CIPN often experience neuropathy symptoms such as pain, tingling, numbness, paresthesia, and dysesthesia, which can lead to significant functional decline and diminished quality of life (QoL). Our prior study showed that more than half of breast cancer survivors who received taxane-based chemotherapy experienced persistent peripheral neuropathy symptoms for a mean duration of 5.6 years after completing chemotherapy. This outcome highlights the importance of developing effective CIPN treatments to improve cancer survivors’ QoL. Identifying nonpharmacological approaches to reduce CIPN symptoms and improve cancer survivors’ outcomes is urgently needed. Acupuncture is a widely used, minimally invasive Traditional Chinese Medicine technique that has shown promising evidence as an effective and safe treatment for CIPN. We hypothesize that acupuncture may reduce CIPN pain and improve overall CIPN symptoms in cancer survivors. Methods: We are conducting a two-arm, parallel randomized clinical trial comparing electroacupunture (EA) versus sham acupuncture (SA) in cancer survivors at Memorial Sloan Kettering Cancer Center, New York, NY. The EA arm includes a total of ten sessions of EA over eight weeks using a standardized, semi-fixed protocol developed by our group based on the previously published pilot study (NCT03183037). The SA arm includes a sham technique that uses a combination of non-acupuncture points and a non-insertion procedure in ten sessions over eight weeks. The primary outcome of this study is the Brief Pain Inventory-Short Form (BPI-SF) average pain item. The secondary outcomes are quantitative sensory testing measures and additional patient-reported outcomes that include the BPI-SF pain interference subscale, Neuropathic Pain Scale (NPS), Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx), CIPN-20, PROMIS Global Health Scale, and Patients’ Global Impression of Change (PGIC). The primary end point is week 12 and the secondary end point is week 24; treatment effects are assessed at baseline and at weeks 4, 8, 12, 18, and 24. Eligibility criteria includes: 1) Moderate-to-severe CIPN pain, defined by a score of 4 or greater on a 0–10 numeric rating scale; 2) completion of neurotoxic chemotherapy at least three months prior to enrollment; and 3) no changes in anti-neuropathy medications within three months of enrollment. We have accrued 30 participants as of February 2022, with a total accrual target of 250 participants. Accrual completion is anticipated by December 2024. Funding resource: NIH R37 CA248563. Clinical trial information: NCT04917796.