Objective To investigate the clinical application value of ultrasound and CT in differential diagnosis of benign and malignant thyroid nodules. Methods 120 patients (138 nodules) with thyroid nodules were selected as study subjects and received ultrasound and CT examination. With the results of pathological examination as the golden standard, the differences inaccuracy, specificity and sensitivity between CT, ultrasound and CT combined with ultrasound in the differential diagnosis of benign and malignant thyroid nodules were evaluated. Results Among the 120 patients with thyroid nodules, there were 89 cases (74.2%) with benign nodules and 31 cases (25.8%) with malignant ones. There were 27 cases of malignant nodules and 85 cases of benign nodules correctly diagnosed by CT combined with ultrasound, and the diagnostic accuracy, specificity and sensitivity were 93.3% , 95.5% and 87.1%, respectively which were significantly higher than those of simple CT examination (80.3%, 82.0%, 77.4%) and simple ultrasound (83.3%, 86.5%, 74.2%) (P<0.05). Conclusion CT combined with ultrasound examination can effectively improve the accuracy of differential diagnosis of benign and malignant thyroid nodules. The tolerance of patients is high, which is of positive significance in reducing the risk of misdiagnosis and missed diagnosis and improving the efficiency of diagnosis.