Introduction Combining immunotherapy with neoadjuvant chemoradiotherapy (neoCRT) has been shown to be safe, achieving a pathological complete response (pCR) rate of 56% in patients with locally advanced oesophageal squamous cell carcinoma (ESCC) in the PALACE-1 trial. This high pCR rate encourages us to explore the feasibility of postponing surgery after immunotherapy combined with neoCRT under active surveillance. This study aims to assess the efficacy, safety and patient-reported quality of life (QOL) of camrelizumab combined with neoCRT and watch-and-wait strategy versus neoCRT followed by surgery in locally advanced resectable ESCC.Methods and analysis The PALACE-3 trial is a multicentre, open-label, randomised non-inferiority trial expected to recruit 356 patients from six high-volume centres in China. The study is planned to start in May 2024 and end in December 2028. Eligible patients will be randomly assigned (1:1 ratio) to either camrelizumab combined with neoCRT and watch-and-wait strategy or neoCRT followed by surgery (standard surgery). In the active surveillance group, patients achieving a clinical complete response (cCR) to camrelizumab combined with neoCRT will undergo active surveillance, while those with residual disease or locoregional recurrence will undergo immediate surgery. Patients in the standard surgery group will proceed to surgery after neoCRT. The primary endpoint is the 3-year overall survival (OS) rate. The secondary endpoints include cCR rate, salvage surgery incidence, objective response rate, adverse events during the neoadjuvant therapy, pCR, tumour regression grade, R0 resection rate, lymph node ratio, perioperative complications, disease-free survival (DFS) and 3-year DFS rate, OS and health-related QOL.Ethics and dissemination This study has been approved by the Ethics Committee of Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital (Shanghai, China), as well as the ethics committees of the following participating centres: National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (Beijing, China); Sichuan Cancer Hospital and Institute, Sichuan Cancer Centre, School of Medicine, University of Electronic Science and Technology of China (Chengdu, China); The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital (Zhengzhou, China); Fujian Medical University Union Hospital (Fuzhou, China). Complete information about the study status, relevant events and results will be regularly updated on the project's webpage on ClinicalTrials.gov. Written informed consent (Supplemental Material) will be obtained from each participant. All research outputs will be published in peer-reviewed journals and presented at national or international conferences.Trial registration number The trial was meticulously registered in advance on 1 April 2024 and can be accessed through the following link: https://www.clinicaltrials.gov/study/NCT06339060. The current protocol version number is V.2.0, and the protocol date is 30 June 2024.