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This study aimed to explore the ability of combination model of ultrasound radiomics score (Rad-score) and the thyroid imaging, reporting and data system by the American College of Radiology (ACR TI-RADS) in predicting benign and malignant thyroid nodules (TNs). Up to 286 radiomics features were extracted from ultrasound images of TNs. By using the lowest probability of classification error and average correlation coefficients (POE + ACC) and the least absolute shrinkage and selection operator (LASSO), we finally selected four features to establish Rad-score (Vertl-RLNonUni, Vertl-GLevNonU, WavEnLH-s4 and WavEnHL-s5). DeLong’s test and decision curve analysis (DCA) showed that the method of combining Rad-score and ACR TI-RADS had the best performance (the area under the receiver operating characteristic curve (AUC = 0.913 (95% confidence interval (CI), 0.881–0.939) and 0.899 (95%CI, 0.840–0.942) in the training group and verification group, respectively), followed by ACR TI-RADS (AUC = 0.898 (95%CI, 0.863–0.926) and 0.870 (95%CI, 0.806–0.919) in the training group and verification group, respectively), and followed by Rad-score (AUC = 0.750 (95%CI, 0.704–0.792) and 0.750 (95%CI, 0.672–0.817) in the training group and verification group, respectively). We concluded that the ability of ultrasound Rad-score to distinguish benign and malignant TNs was not as good as that of ACR TI-RADS, and the ability of the combination model of Rad-score and ACR TI-RADS to discriminate benign and malignant TNs was better than ACR TI-RADS or Rad-score alone. Ultrasound Rad-score might play a potential role in improving the differentiation of malignant TNs from benign TNs.