Objective: To investigate the clinical value of high-frequency color Doppler ultrasound (HFCDU) in the differential diagnosis of benign thyroid nodules and thyroid carcinoma. Methods: A total of 92 patients treated in Pudong New Area People's Hospital for thyroid nodules from June 2015 to July 2016 were recruited as subjects. All of them underwent HFCDU tests before surgery and received the postoperative pathological diagnosis which was used as the gold standard. The results obtained from HFCDU and pathological examination for the differential diagnosis of benign and malignant thyroid nodules were compared and analyzed. Meanwhile, the size, shape, boundary, internal echo, internal and surrounding blood flow signal of these two types of nodules were examined for comparison. Results: There were 107 nodules in 92 patients. The sensitivity, specificity, and accuracy of HFCDU were 93.55%, 86.67% and 90.65% respectively. The value of the areas under the curve (AUC) calculated from the receiver operating characteristic (ROC) curve was 0.923, and the 95% confidence interval (CI) was 0.886-0.967. The differences in boundary, shape, aspect ratio, internal echo, posterior echo, calcification and other indices between benign and malignant thyroid nodules were significant (P<0.05). The result from the multi-variant logistic regression analysis showed that factors such as unclear boundary, irregular shape, aspect ratio > 1, blood flow > grade 2, and uneven internal echo were all correlated with thyroid nodule malignancy. Conclusion: HFCDU can be applied clinically for the differential diagnosis of benign and malignant thyroid nodules as it has high sensitivity, specificity and can present clear imaging features.