Objective To analyze the value of contrast-enhanced ultrasonography (CEUS), MSCT and fine needle aspiration cytology (FNAC) in the diagnosis of benign and malignant thyroid nodules. Methods 90 patients (95 nodules) with thyroid disease who were admitted to the hospital from July 2016 to November 2017 were studied. Among them, 40 benign nodules and 55 malignant nodules were confirmed by pathological examination. All of them were examined by CEUS, MSCT and FNAC. The imaging features of the three methods were analyzed, and the diagnostic efficiencies of CEUS, MSCT and FNAC were evaluated. Results Imaging findings of both CEUS and MSCT for benign thyroid nodules were characteristic. The specificity, accuracy, positive predictive value and negative predictive value of FNAC for the diagnosis of thyroid nodules were higher than those of CEUS or MSCT. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of combined detection of CEUS, MSCT and FNAC were higher than those of single detection (P<0.05). Conclusion CEUS, MSCT and FNAC are of high diagnostic value for benign and malignant thyroid lesions. The specificity and accuracy of FNAC are high. The combined detection of the three is helpful to improve the diagnostic efficiency.