Objective To summarize the ultrasonographic and pathological features of benign thyroid nodules in thyroid imaging reporting and data system (TI-RADS) 4 class. Methods The preoperative ultrasonographic features and pathological features of 46 patients (52 nodules) with TI-RADS 4 class benign thyroid nodules who got treatment in Affiliated Hospital of Nanjing University of Traditional Chinese Medicine between June 2016 and June 2017 were retrospectively analyzed. Results Among the 52 thyroid nodules, 32 nodules (61.54%) were categorized as TI-RADS 4A, 12 nodules (23.08%) were categorized as TI-RADS 4B, and 8 nodules (15.38%) were categorized as TI-RADS 4C. On ultrasonographic images, the 52 thyroid nodules showed hypoechogenicity (90.38%), solid or predominantly solid (98.08%), nodules>1 cm in diameter (61.54%), defined margin (63.46%), microcalcification (50.00%), abundant or pointy blood flow (65.39%), morphological rule (90.38%), aspect ratio≤1 (92.31%), and no suspicious lymph nodes (86.54%). On histology, these thyroid nodules revealed nodular goiter with fibrosis or calcification (38.46%), nodular goiter with adenoma (30.77%), nodular goiter (9.61%), Hashimoto’s thyroiditis (17.31%), and thyroid follicular adenoma (3.85%). Conclusion Nodular goiter (thyroid nodules with fibrosis, calcification or adenomatoid hyperplasia), Hashimoto’s thyroiditis, and thyroid follicular adenoma will lead to malignant signs on ultrasonographic images, we should refer to other examination methods to make combinated evaluation.