Objective: The purpose of this study was to use a computer-aided diagnosis (CAD) system based on the Thyroid Imaging, Reporting, and Data System (TI-RADS) to improve the diagnostic performance of thyroid cancer by analyzing clinical ultrasound imaging data. Methods: A retrospective diagnostic study of ultrasound image sets was conducted at five hospitals in China. A CAD system based on TI-RADS was applied in this study, and the diagnostic performance of CAD system was tested through multi-center data. The performance of the CAD system was compared with the consensus of three experienced radiologists. The interobserver agreement for cancer diagnosis was calculated between the CAD system and the consensus of the three experienced radiologists. Results: The CAD system performed well in the diagnosis of thyroid cancer, with an area under the curve (AUC) value of 0.902 (95% CI: 0.884-0.918), and obtained results similar to those of the three experienced radiologists. The CAD system performed better in the internal test set than in the external test set (AUC: 0.930 vs 0.877, respectively). The performance of the CAD system in the diagnosis of thyroid cancer for nodules of different sizes (<1 cm, 1-2 cm and >= 2 cm) was basically similar (accuracy: 84.6% vs 85% vs 84.2%). The CAD system can recognize 15 ultrasound features of thyroid nodules, most of which reached the level of 3 experienced radiologists (12/15, 85%). Conclusion: The CAD system achieved an improved AUC and similar sensitivity and specificity in the diagnosis of thyroid cancer compared with the consensus of experienced radiologists.