Objective To Explore the Efficacy and Safety of Intensity-Modulated Radiation Therapy (IMRT) Combined with Trastuzumab and Platinum-Based Regimens in the Treatment of Resectable Locally Advanced Esophageal Squamous Cell Carcinoma (ESCC). Methods Collecting Data on 120 Cases of Locally Advanced Esophageal Squamous Cell Carcinoma (ESCC) Patients Who Received Neoadjuvant Therapy at Zhongshan Hospital Affiliated with Xiamen University from December 2019 to November 2022. 120 ESCC patients were divided into control group (n=60) and observation group (n=60) according to different treatment methods. The control group was treated with treprizumab combined with paclitaxel and carboplatin, and the observation group was treated with IMRT on this basis. After treatment, evaluate whether surgery can be performed, and compare the R0 resection rate, pathological complete response (pCR) rate, main pathological response (MPR) rate, objective response rate (ORR), and disease control rate (DCR) of the two groups. The perioperative related indexes of the two groups were observed, and the long-term efficacy and safety of the two groups were compared after 24 months of follow-up. Results The completion rate of new adjuvant therapy in both groups reached 100%. The R0 resection rate, pCR rate, MPR rate, ORR rate, DCR rate and DCR rate in the observation group were 91.67%, 40.00%, 61.67%, 86.67% and 96.67%, respectively, which were significantly higher than those in the control group (P<0.05). There was no significant difference between the observation group and the control group in terms of operation time, intraoperative blood loss and postoperative complications (P>0.05). There was no significant difference in progression free survival rate and overall survival rate between the two groups after 24 months of follow-up (P>0.05). There was no significant difference between the two groups in the occurrence of anemia, nausea, vomiting, leukopenia and other adverse reactions (P>0.05). Conclusion The new adjunctive therapy mode of IMRT combined with treprizumab plus paclitaxel plus carboplatin can improve the clinical efficacy of locally advanced resectable ESCC with good safety