Objective To explore the malignant risk and clinical diagnostic value of contrast-enhanced ultrasonography(CEUS)for thyroid imaging reporting and data system(TI-RADS)class 4 thyroid nodules. Methods The characteristics of nodules in 226 thyroid patients were analyzed and classified according to Kwak criteria. TI-RADS 4A, 4B and 4C nodules were included in the study. All nodules were examined by CEUS. The results of CEUS were compared with those of pathology. Results Of 226 TI-RADS 4 nodules, 106 were malignant and 120 were benign by CEUS, 110 were malignant and 116 were benign by pathology after operation. The accuracy, sensitivity, specificity, positive predictive value and negative predictive value of CEUS in the diagnosis of 4 types of nodules were 91.15%, 89.09%, 93.10%, 89.91% and 89.74%, respectively.The results of CEUS in the diagnosis of 4 types of nodules were consistent with those of pathology. The Kappa value was 0.823 (P < 0.001).The actual malignant rates of CEUS in the diagnosis of 4A, 4B and 4C nodules were 14.06% (9/64), 47.53% (48/101) and 86.89% (53/61), respectively.Conclusion CEUS examination has high diagnostic value for TI-RADS class 4 thyroid nodules. It is helpful to guide the clinical follow-up decision-making of TI-RADS class 4 thyroid suspected nodules.