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Objective To evaluate the influencing factors for severe absolute lymphatic count (ALC) reduction during concurrent chemoradiotherapy (CCRT) in patients with esophageal squamous cell carcinoma (ESCC), to develop a predictive model for severe ALC reduction during CCRT in patients with ESCC, and to validate its efficacy. Methods Clinical baseline data, radiotherapy regimen, and radiotherapy dosimetry parameters were collected from 286 ESCC patients who underwent CCRT. Trends in ALC during CCRT were analyzed based on pre-treatment ALC and weekly ALC during treatment. Patients were divided into the severe ALC reduction group and non-severe ALC reduction group according to whether severe ALC reduction occurred during CCRT. We compared the above information between the two groups, and screened the independent risk factors for severe ALC reduction during CCRT in ESCC patients by multifactorial Logistic regression analysis, constructed the risk prediction model based on risk factors, and plotted a nomogram (nomogram model). Receiver operating characteristics (ROC) curve, consistency index (C-index), calibration curve, and decision analysis (DCA) curve were used to assess the discrimination, consistency, calibration, and clinical applicability of the nomogram model. Results ESCC patients showed a gradual decrease in ALC during CCRT (P＜0. 05). Statistically significant differences were found in BMI, pre-treatment ALC, mean vertebral dose (MVD), and estimated dose of circulating immune cells (EDIC) between the two groups (all P＜0. 05). BMI (OR=0. 829, 95%CI:0. 760-0. 900), pretreatment ALC (OR=0. 412, 95% CI:0. 253-0. 648), MVD (OR=1. 079, 95% CI:1. 011-1. 155) and EDIC (OR=1. 711, 95%CI:1. 422-2. 292) were independent influencing factors for severe ALC reduction during CCRT in ESCC patients (all P＜0. 05). A nomogram model was constructed based on the above risk factors. The area under the ROC of the nomogram model in predicting the occurrence of severe ALC reduction during CCRT was 0. 799 (95% CI:0. 748-0. 850), the C-index was 0. 789, and the predicted risk of ALC reduction was consistent with the risk of the actual occurrence;the prediction of severe ALC reduction had good clinical applicability in the probability range of 0. 25 to 0. 90. Conclusions The independent influencing factors for severe ALC reduction during CCRT in ESCC patients are BMI, pretreatment ALC, MVD, and EDIC, and the nomogram model for predicting severe ALC reduction during CCRT in ESCC patients based on the above mentioned influencing factors has good differentiation, consistency, calibration, and clinical applicability. [ABSTRACT FROM AUTHOR]