Background: The objective of conversion therapy is to convert unresectable locally advanced esophageal cancer into resectable condition. Chemoradiotherapy is the standard treatment; however, radiotherapy may increase surgical difficulty and complications. Recently, immunotherapy has shown significant efficacy in advanced esophageal cancer, but its specific role in neoadjuvant therapy remains unclear. This study aims to investigate the efficacy, safety, and short-term perioperative outcomes of using domestically produced PD-1 inhibitors combined with chemotherapy as neoadjuvant therapy for locally advanced ESCC. Methods: 46 patients who received neoadjuvant treatment with domestically produced PD-1 inhibitors combined with chemotherapy were selected. The retrospective analysis included patient data on dosing regimens, imaging results, pathological findings, surgical details, and adverse events associated with treatment for locally advanced ESCC. Results: After neoadjuvant chemoimmunotherapy the T, N, and TNM stages significantly regressed. The objective response rate (ORR) of 67.4% and the disease control rate (DCR) of 100%. The treatment’s safety profile was acceptable, with toxicity remaining manageable and no fatalities attributable to the therapy. 45 patients (97.8%) achieved R0 resection. The rates of major pathological response (MPR) and pathological complete response (pCR) were 56.5% and 17.4%, respectively. The rate of lymphovascular invasion was 10.9%, the rate of nerve invasion was 26.1% and the lymph node metastasis rate was 30.4%. These results indicated significant radiologic and pathologic response. Conclusion: Our results indicate that neoadjuvant chemoimmunotherapy represents a viable and promising treatment for locally advanced ESCC, without increasing surgical complexity or the risk of complications. These findings justify further studies with larger sample sizes and extended follow-up to confirm its long-term efficacy and safety.