Objective:To explore the diagnostic value of contrast-enhanced ultrasound combined with fine-needle aspiration biopsy and BRAF gene detection for TI-RADS category 4 nodules.Methods:The clinical datas of 80 patients who underwent surgery in the First Affiliated Hospital, Zhejiang University School of Medicine and Lishui People′s Hospital and diagnosed with TI-RADS 4 thyroid nodules from January 2019 to January 2020 were retrospectively analyzed. All patients received contrast-enhanced ultrasound combined fine-needle aspiration biopsy and BRAF gene detection, the ROC curves were plotted, the area under the ROC curve(AUC) and the best diagnostic cut-off values were calculated, and the application value of ultrasound-enhanced contrast, fine-needle aspiration biopsy and BRAF gene detection were compared.Results:Based on the results of pathological diagnosis, in diagnosing TI-RADS 4 thyroid nodules, the sensitivity, specificity and accuracy were 77.61%, 70.97% and 75.51% for contrast-enhanced ultrasound, respectively; 80.60%, 74.19%, and 78.57% for ultrasound-guided fine-needle aspiration biopsy, respectively; 79.10%, 96.77%, and 84.69% for the BRAF gene test, respectively; and 98.51%, 70.97% and 89.80% for the combined diagnosis, respectively. The AUC was 0.790 for contrast-enhanced ultrasound, and 0.774 for ultrasound-guided fine-needle aspiration biopsy, 0.799 for BRAF genetic testing, and 0.847 for combined testing. The diagnostic value of combined diagnosis was significantly higher than other diagnostic methods ( P<0.05). Conclusions:Contrast-enhanced ultrasound combined with fine-needle aspiration biopsy and BRAF gene detection is valuable for the diagnosis of TI-RADS 4 class thyroid nodules and improves the preperative diagnosis.