Objective To explore the value of shear wave elastography (SWE) combined with Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) classification guidelines in the differential diagnosis of thyroid nodules. Methods The data of 176 patients with thyroid nodules were retrospectively analyzed, with a total of 179 nodules, including 78 benign nodules and 101 malignant nodules. There were 77 small nodules (≤10 mm) and 102 large nodules (>10 mm). With crude needle puncture or surgical pathological results as the “gold standard”, the consistency between conventional ultrasonic C-TIRADS classification diagnosis, SWE and their combined diagnosis and “gold standard” was analyzed, and the working characteristic curve of subjects was drawn to analyze the diagnostic efficacy of conventional ultrasonic C-TIRADS classification diagnosis, SWE and their combined diagnosis. Results The maximum value (SWEmax), the minimum value (SWEmin), the mean value (SWEmean) and the standard deviation (SWESD) of SWE Young's modulus of benign nodules were smaller than those of malignant nodules, and the difference was statistically significant (P<0.05). With regard to malignant nodules, the SWEmax, SWEmean, SWEmin, and SWESD values of the large nodule group were higher than the small nodule group, and the difference was statistically significant (P<0.001). The sensitivity, specificity, accuracy, area under curve (AUC) and Kappa values of C-TIRADS guideline diagnosis were 97.03%, 60.26%, 81.0%, 0.786 and 0.597, respectively. The sensitivity, specificity, accuracy, AUC, and Kappa values of SWE diagnosis were 89.11%, 87.18%, 88.3%, 0.881 and 0.762, respectively. The kappa value, sensitivity, specificity, accuracy,and AUC of the combined diagnosis were 0.874, 99.01%, 88.46%, 94.4%, and 0.937, respectively. Conclusion Young’s modulus values of large and small malignant nodules were higher than those of large and small benign nodules. The combination of SWE and C-TIRADS guidelines in the diagnosis of thyroid nodules can further improve the sensitivity, specificity, accuracy, which can be extended to clinical practice.