Objective: To investigate the contrast-enhanced ultrasonography (CEUS) imaging features of Chinese Thyroid Imaging Reports and Data System (C-TIRADS) 4 types of benign and malignant thyroid nodules and their correlation with serine/threonine-specific kinase (BRAF) gene.Methods: A total of 126 patients with thyroid nodules who underwent CEUS examination in our hospital from January 2020 to January 2022 and were confirmed by surgery and pathology were selected, and BRAF gene mutation detection was performed after surgery. According to the C-TIRADS guidelines, it was divided into C-TIRADS 4A (52 cases), C-TIRADS 4B (36 cases) and C-TIRADS 4C (38 cases). The CEUS imaging features and BRAF gene mutation of three types of thyroid nodules were compared, and the receiver operating characteristic (ROC) curve was drawn to evaluate the CEUS imaging characteristics, BRAF gene mutation alone and combined diagnosis of C-TIRADS type 4 malignant thyroid nodules diagnostic performance. Spearman correlation was used to analyze the correlation between CEUS imaging features of C-TIRADS category 4 malignant thyroid nodules and BRAF gene mutation.Results: The pathological results of C-TIRADS 4A thyroid nodules were thyroid adenoma (21 cases) and nodular goiter (31 cases); the pathological results of C-TIRADS 4B/C thyroid nodules were all papillary thyroid carcinoma (36/ 38 cases). Most of C-TIRADS 4 B/C thyroid nodules showed low enhancement (66.67%, 73.68%), heterogeneous enhancement (94.44%, 89.47%), concentric enhancement (97.22%, 89.47%), and accounted for The proportions were significantly higher than those of C-TIRADS class 4A (P<0.05). BRAF gene mutation was found in 58 of 126 thyroid nodules, and the incidence rate was 46.03%. The postoperative pathological results were all papillary thyroid carcinoma. The proportion of BRAF gene mutation in C-TIRADS 4 B/C thyroid nodules was significantly higher than that in C-TIRADS 4A (P<0.05). By drawing the ROC curve, it was found that CEUS imaging features combined with BRAF gene mutation had the highest AUC (0.973), and the highest sensitivity (100%) and specificity (94.60%) in the diagnosis of C-TIRADS type 4 malignant thyroid nodules, and the difference was statistically significant Academic significance (P<0.05). CEUS imaging features of C-TIRADS class 4 malignant thyroid nodules (low enhancement, heterogeneous enhancement, and centripetal enhancement) were significantly positively correlated with BRAF gene mutation (P<0.05). Conclusion: CEUS imaging features combined with BRAF gene mutation can help improve the differential diagnosis value of C-TIRADS 4 malignant thyroid nodules, and CEUS imaging features have a significant positive correlation with BRAF gene mutation, indicating that CEUS imaging features can be used to a certain extent. Reflecting the biological behavior of C-TIRADS category 4 malignant thyroid nodules can help to improve its differential diagnosis value, and further provide a more scientific imaging basis for clinicians to make qualitative judgments.