Objective To analyze the diagnostic value of artificial intelligence ultrasonic assisted diagnosis system (AI-UADS) combined with contrast-enhanced ultrasound (CEU) for American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) class 4 nodules. Methods A total of 84 patients with ACR TI-RADS class 4 thyroid nodules admitted to the hospital were enrolled between March 2018 and March 2022. All underwent AI-UADS and CEU examinations. The diagnostic value of the two methods and combined detection for benign and malignant ACR TI-RADS class 4 nodules was compared. Results There were 92 nodules in the 84 patients, including 17 malignant nodules (18.48%). CEU showed that there were 14 malignant nodules, its sensitivity, specificity, accuracy, positive predictive value, negative predictive value and kappa value in the diagnosis of malignant nodules were 82.35%, 81.33%, 81.52%, 50.00%, 95.31% and 0.509, respectively. AI-UADS showed that there were 15 malignant nodules, and its sensitivity, specificity, accuracy, positive predictive value, negative predictive value and kappa value were 88.24%, 82.67%, 83.70%, 53.57%, 96.88% and 0.567, respectively. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value and kappa value of combined detection were 82.35%, 93.33%, 91.30%, 73.68%, 95.89% and 0.724, respectively. The specificity of combined detection was higher than that of CEU and AI-UADS (χ_²=0.027, 0.044, P<0.05). Conclusion Both AI-UADS and CEU have good diagnostic efficiency for benign and malignant ACR TI-RADS class 4 thyroid nodules, and the combined detection can effectively improve clinical specificity.