Abstract: Objective To investigate the efficacy and safety of first-line camrelizumab combined with chemotherapy followed by sequential radiotherapy in patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC).Methods Clinical data were collected from patients with unresectable locally advanced ESCC who were admitted in the Affiliated Hospital of Xuzhou Medical University from January 10, 2022 to February 10, 2024. Thirty-one patients received first-line camrelizumab plus nab-paclitaxel and nedaplatin followed by sequential radiotherapy (sequential radiotherapy group), while another 31 patients received first-line camrelizumab plus nab-paclitaxel and nedaplatin (immunotherapy plus chemotherapy group). Their clinical efficacy and the incidence of adverse reactions were evaluated.Results In the sequential radiotherapy group, the objective response rate (ORR) was 67.7%, the median progression-free survival (mPFS) was 13.2 months and the incidence of grade ≥3 adverse reactions was 29.0% (9/31). In the immunotherapy plus chemotherapy group, the ORR was 41.9% and the mPFS was 8.2 months, while the incidence of grade ≥3 adverse reactions was 41.9% (13/31).Conclusions First-line camrelizumab combined with chemotherapy followed by sequential radiotherapy shows better efficacy in patients with unresectable locally advanced ESCC, with adverse reactions remaining controllable.