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Background: This study aimed to propose a machine learning model to predict the local response of resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) treated by neoadjuvant chemoradiotherapy (NCRT) using pretreatment 18-fluorodeoxyglucose positron emission tomography (FDG PET) images. Methods: The local responses of 98 patients were categorized into two groups (complete response and noncomplete response). We performed a radiomics analysis using five segmentations created on FDG PET images, resulting in 4250 features per patient. To construct a machine learning model, we used the least absolute shrinkage and selection operator (LASSO) regression to extract radiomics features optimal for the prediction. Then, a prediction model was constructed by using a neural network classifier. The training model was evaluated with 5-fold cross-validation. Results: By the LASSO analysis of the training data, 22 radiomics features were extracted. In the testing data, the average accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve score of the five prediction models were 89.6%, 92.7%, 89.5%, and 0.95, respectively. Conclusions: The proposed machine learning model using radiomics showed promising predictive accuracy of the local response of LA-ESCC treated by NCRT.