BACKGROUND: Camrelizumab combined with chemotherapy has shown significant clinical benefits in the first-line treatment of advanced esophageal squamous cell cancer (ESCC). Despite promising results from randomized trials, there is a need for real-world evidence to understand the broader applicability and long-term outcomes of neoadjuvant treatments in diverse patient populations with ESCC. This study aimed to evaluate the efficacy and safety of neoadjuvant camrelizumab combined with chemotherapy in patients with resectable locally advanced ESCC in a real-world setting. METHODS: We retrospectively reviewed clinical data from 83 patients with locally advanced, potentially resectable ESCC who received neoadjuvant camrelizumab combined with docetaxel, oxaliplatin, and S1 chemotherapy at Xijing Hospital of Digestive Diseases, Fourth Military Medical University from March 2020 to May 2023. Inclusion criteria were based on clinical stage, histological confirmation, and patient tolerance. Baseline clinical characteristics were assessed using standard diagnostic tools. Treatment involved three cycles of camrelizumab combined with chemotherapy, with efficacy and safety evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Tumor downstaging, survival outcomes, and safety were assessed. RESULTS: The median age of patients was 61 years (range, 46-75 years), and tumors were predominantly located in the middle (n=49, 59.04%) and lower (n=23, 27.71%) regions of the esophagus. Most patients were diagnosed at stages III-IV (55.42% and 38.55%, respectively), and all of the patients completed neoadjuvant treatment. Additionally, 24 (28.92%) patients achieved complete response (CR), 40 (48.19%) patients achieved partial response (PR), and 9 (10.84%) patients achieved stable disease (SD). The objective response rate (ORR) was 77.11% (64/83), and the disease control rate (DCR) was 87.95% (73/83). Of the 14 patients who underwent surgery, the R0 resection rate was 100%, and 28.57% (4/14) achieved pathological CR (pCR). The median follow-up time was 31.0 months, and the 3-year overall survival (OS) rate was 56.9%. The incidence of grade ≥3 adverse events was 6.02% (5/83). No deaths occurred. CONCLUSIONS: While our real-world data suggest potential benefits of neoadjuvant camrelizumab plus chemotherapy in locally advanced ESCC, the absence of a control group limits the generalizability of these findings. Further randomized studies are needed to validate these results.