ABSTRACT: Potential use of sonographic TI-RADS classification combined with circulating miRNA expression profiling in the diagnosis of thyroid nodules was explored. Retrospective analysis was performed on clinical data of 121 patients with thyroid nodules. The biopsy specimens of patients obtained through ultrasound-guided aspiration and blood specimens were evaluated in Zhengzhou Central Hospital Affiliated to Zhengzhou University from June 2018 to June 2019. In addition, the blood specimen test results of 121 healthy volunteers (control group) who underwent physical examination were retrospectively analyzed. Results of sonographic TI-RADS classification and circulating miRNA expression profiling were compared with the pathological results. Of the 212 nodules, 2 fell into TI-RADS category 2 and were diagnosed as benign. Malignant nodules accounted for 4.35, 37.14, 84.78, 93.33 and 96.77% of those nodules that fell into TI-RADS categories 3, 4a, 4b, 4c and 5, respectively. Of the 121 patients, 92.55% had with nodular goiter, 3.31% had inflammatory nodules, 2.48% toxic nodular goiter, 0.83% thyroid cysts and 0.83% thyroid tumors. A nodule that fell into a higher TI-RADS classification category had a higher risk of malignancy. The expression levels of miRNA146b, miRNA187, miRNA375, miRNA-222-3p and miRNA-151a-5p were higher, while the level of miRNA138 was lower, in patients with either benign or malignant thyroid nodules compaed to those in the control group. The expression levels of miRNA146b, miRNA187, miRNA375, miRNA-222-3p and miRNA-151a-5p were higher, while the level of miRNA138 was lower, in patients with malignant thyroid nodules than those in patients with benign thyroid nodule (P<0.05). The AUC of the combined diagnostic method was 0.973, which was significantly different from the AUCs of the individual diagnostic method (P<0.05). In conclusion, sonographic TI-RADS classification combined with circulating miRNA expression profiling can improve the diagnosis of thyroid nodules.