Objective To investigate the application of US-FNAB combined with BRAFV600E gene detection and angiography in the diagnosis of C-TIRADS 4 thyroid nodules. Methods A total of 101 patients (104 nodules in total) with thyroid nodules were selected. According to the routine ultrasonic characteristics of thyroid nodules, C-TIRADS 4thyroid nodules were selected according to C-TIRADS criteria. All cases underwent routine ultrasound、US-FNAB、BRAF V600E gene detection and contrast-enhanced ultrasound examination, and the pathological results were used as the "gold standard" of this study. Kappa consistency test was used to evaluate the consistency of US-FNAB and its combined BRAF V600E gene detection and contrast-enhanced ultrasound with postoperative pathological results, and their sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated. To evaluate the diagnostic efficacy of US-FNAB and its combination with BRAF V600E gene detection and contrast-enhanced ultrasound in C-TIRADS 4thyroid nodule. Results In the Kappa consistency test method, the respective Kappa values were 0.76(US-FNAB), 0.86 (US-FNAB combined with BRAFV600E gene), 0.88 (US-FNAB combined with contrast-enhanced ultrasound), 0.90(US-FNAB combined with BRAF V600E gene and contrast-enhanced ultrasound), all＞0.75; The sensitivity, specificity, positive predictive value, negative predictive value and accuracy respectively were US-FNAB: 93.3%, 82.8%, 93.3%, 82.8%, 90.4%; US-FNAB combined BRAF V600E gene test: 96.0%, 89.7%,96.0%, 89.7%, 94.2%; US-FNAB: combined contrast-enhanced ultrasound: 97.3%, 89.7%, 96.0%, 92.9%, 95.2%. US-FNAB combined with BRAF V600E gene testing and contrast-enhanced ultrasound:97.3%, 93.1%, 97.3%, 93.1%, 96.2%. Conclusion US-FNAB combined with BRAFV600E gene detection and contrast-enhanced ultrasound have high diagnostic value for C-TIRADS type 4 thyroid nodules, which is an effective method for clinical treatment and prognosis assessment