Abstract: Objective To investigate the differential value of multiple ultrasonography in the detection of benign and malignant thyroid nodules with diameter. Methods Total 1 393 patients with thyroid nodules were examined by ultrasound. The ultrasound features (Nodular nature, margins, calcifications, nodule morphology, type of echoes, signs of lymph node metastasis, and blood flow) were analyzed by TI-RADS classification system and compared with the pathological results for statistical analysis. Results Of the 1 393 patients, 913 were malignant and 479 were benign. More malignant nodules showed irregular nodules, unclear boundaries, the internal hypoechoic or hypoechoic low echo, aspect ratio ≥ 1, tiny calcification, nodules can be seen inside the rich blood flow. Logistic regression analysis showed irregular nodules, unclear boundary, internal hypoechoic or hypoechoic echo, A/T>1, microcalcifications and blood flow (Ⅲ) as the dangerous ultrasound signs of malignant nodules. The results showed that the diagnostic specificity, sensitivity, positive predictive value and negative predictive value were 78.3%, 82.4%, 72.3%, 84.5%, respectively, according to any of the 6 signs in the combined detection of multiple ultrasonographic signs. Its accuracy reached 79.1%. Conclusion Combined detection of multiple ultrasonographic signs can significantly improve the specificity of diagnosis of malignant nodules and reduce the incidence of misdiagnosis. In clinical application, if any combination of three ultrasound signs is found, malignant thyroid nodules should be highly suspected, so patients should be advised to do Further examination.