Objective: To investigate the value of contrast-enhanced ultrasound parameters and elastography strain rate ratio in the differential diagnosis of benign and malignant thyroid nodules, and to analyze their relationship with angiogenesis genes. Methods: 136 patients with thyroid nodules were selected as the research objects. The study period was from May 2017 to March 2020. A total of 102 cases of benign nodules and 34 cases of malignant nodules were diagnosed by pathological examination. All patients were given contrast ultrasound and Elastography was used to detect and obtain the contrast-enhanced ultrasound parameters and the ratio of elastography strain rate, and the Pearsom method was used to analyze its relationship with angiogenesis genes. Results: The positive predictive value, negative predictive value, sensitivity, specificity, and accuracy of contrast-enhanced ultrasound were all higher than elastography, while the misdiagnosis rate and missed diagnosis rate were lower than elastography (all P<0.05).The AUC and Peak of malignant thyroid nodules are lower than that of benign nodules, while the ratio of Tp and elastography strain rate is higher than that of benign nodules (P<0.05); the MTT of malignant thyroid nodules is the same as that of benign nodules (P>0.05) .The AUC value of the area under the ROC curve of contrast-enhanced ultrasound was (0.961, P＜0.05). The AUC value of the area under the ROC curve of elastography was divided into (0.799, P＜0.05).The AUC value of the area under the ROC curve of the elastography strain rate ratio is (0.995, P<0.05), the sensitivity is 100.00%, the specificity is 94.10%, and the Youden index is 0.941.The area under the ROC curve of the comprehensive parameters of Tp, AUC, Peak, and contrast-enhanced ultrasound AUC value is (0.915/0.978/0.972/0.988, P＜0.05), sensitivity (91.20%/97.10%/100.00%/100.00%), specificity(98.00%/96.10%/90.20%/91.20%),Youden Index (0.892/0.932/0.902/0.912).Conclusion: The decrease of contrast-enhanced parameters of malignant thyroid nodules and the increase of elastography strain rate ratio are directly related to the exuberance of tumor angiogenesis genes, which can be used as reliable indicators for judging the malignancy of thyroid nodules.