Objective To investigate the value of real-time ultrasound elastography (UE) combined with TI-RADS standard for differential diagnosis of thyroid nodules. Methods 125 thyroid nodule patients confirmed by surgery and pathology were selected in our department, from January 2015 to December 2016, and 190 nodules were finally involved. The patients were subsequently divided into two groups (nodules <1cm group and ≥ 1cm group). After the conventional ultrasound and UE examination, TI-RADS were used to evaluate the nodule characteristics. The working characteristic curves of UE and TI-RADS were constructed to analyze the applicability of each strategy for differential diagnosis of thyroid nodules. Results The sensitivity and specificity of UE in diagnosing thyroid nodules were significantly higher than TI-RADS, while the diagnostic accuracy of TI-RADS was higher than that of UE in ≥1cm group. Either method alone was significantly lower in sensitivity, specificity and accuracy than combined diagnosis. The area under ROC curve of UE was significantly larger than TI-RADS. The AUC of the combined diagnosis was statistically higher than each alone (P <0.05). Conclusion The coordination of TI-RADS standard and UE have great accuracy and diagnostic efficiency for benign and malignant thyroid nodules. The combination can make up for the shortcomings and deficiencies of single technology in differential diagnosis. UE combined with TI-RADS is of great value for clinical application and further promotion.