Introduction Oesophageal cancer (EC) presents a substantial global health challenge, ranking eighth in incidence and sixth in cancer-related mortality. Oesophageal squamous cell carcinoma (ESCC) is the primary subtype and accounts for approximately 90% of cases in Asia. Despite treatment advances, the 5-year survival rate remains modest at 10%-30%. Immune checkpoint inhibitors, exemplified by KEYNOTE-590 and CheckMate 577 trials, have reshaped EC therapeutic landscapes. Our study addresses the critical gap in understanding the real-world impact of PD-1 (Programmed Death-1) inhibitors, conducting a multicentre, real-world, observational cohort analysis focused on ESCC. This research endeavours to provide practical insights into PD-1 treatment for EC, facilitating informed clinical decision-making and optimising patient outcomes in diverse healthcare settings.Methods and analysis This multicentre study includes patients diagnosed with histopathologically confirmed ESCC who have consented to treatment with PD-1 inhibitors. It is structured into two distinct segments: Part A, characterised by its retrospective nature, and Part B, representing the prospective arm. Within both parts, four stratified cohorts are delineated, comprising Cohort 1 (preoperative neoadjuvant/conversion therapy), Cohort 2 (postoperative adjuvant therapy), Cohort 3 (first-line therapy for advanced ESCC) and Cohort 4 (>= 2 lines of therapy for advanced ESCC). The primary endpoint is the objective response rate in diverse treatment cohorts. Secondary endpoints include pathologic complete response rate, disease-free survival, progression-free survival, overall survival, adverse events, immune-related adverse events, quality of life and the intricacies of immunotherapy patterns and hyperprogression. Furthermore, exploratory endpoints scrutinise potentially predictive biomarkers, as well as the clinical and genomic characteristics inherent to ESCC patients if possible. The study endeavours to enrol 417 participants, subject to a comprehensive 5-year follow-up period. We will collect and analyse real-world data from Chinese ESCC patients treated with PD-1 inhibitors to observe and describe the efficacy and safety of PD-1 inhibitors in Chinese patients with ESCC at various treatment stages.Methods and analysis This multicentre study includes patients diagnosed with histopathologically confirmed ESCC who have consented to treatment with PD-1 inhibitors. It is structured into two distinct segments: Part A, characterised by its retrospective nature, and Part B, representing the prospective arm. Within both parts, four stratified cohorts are delineated, comprising Cohort 1 (preoperative neoadjuvant/conversion therapy), Cohort 2 (postoperative adjuvant therapy), Cohort 3 (first-line therapy for advanced ESCC) and Cohort 4 (>= 2 lines of therapy for advanced ESCC). The primary endpoint is the objective response rate in diverse treatment cohorts. Secondary endpoints include pathologic complete response rate, disease-free survival, progression-free survival, overall survival, adverse events, immune-related adverse events, quality of life and the intricacies of immunotherapy patterns and hyperprogression. Furthermore, exploratory endpoints scrutinise potentially predictive biomarkers, as well as the clinical and genomic characteristics inherent to ESCC patients if possible. The study endeavours to enrol 417 participants, subject to a comprehensive 5-year follow-up period. We will collect and analyse real-world data from Chinese ESCC patients treated with PD-1 inhibitors to observe and describe the efficacy and safety of PD-1 inhibitors in Chinese patients with ESCC at various treatment stages.Ethics and dissemination Ethical approval was provided by the Ethics Committee for Medical Research and New Medical Technology of Sichuan Cancer Hospital, China (Approval No. SCCHEC-02-2023-096). Each participating hospital has applied for research permission from the Institutional Review Board of its unit. We will disseminate the results through peer-reviewed journals and academic conferences.Trial registration number ChiCTR2300078657.