Objective: To investigate the value of polygenic detection and strain elastography in the differential diagnosis of benign and malignant thyroid nodules with uncertain cytology. Methods: A total of 124 patients with thyroid nodules were selected as the research subjects. The selection time was from May 2019 to June 2020. There were 136 thyroid nodules confirmed by pathological results and diagnosed as IC by cytology (Bethesda Ⅲ, Ⅳ, Ⅴ categories). ), 91 malignant nodules and 45 benign nodules were detected by polygene and strain elastography, and the positive predictive value and negative predictive value were calculated by the four-table method; the ROC curve model was used to analyze the polygene detection, strain AUC value, sensitivity and specificity of elastography and two combined differential diagnosis of benign and malignant thyroid nodules with uncertain cytology.Results: After polygenic detection of 124 patients with thyroid nodules, the positive predictive value was 89.13% and the negative predictive value was 79.55%. Compared with the gold standard, the consistency was general (Kappa=0.683, P<0.05). After imaging examination, the positive predictive value was 78.88% and the negative predictive value was 56.52%, which showed poor agreement compared with the gold standard (Kappa=0.356, P<0.001). After the two combined examinations, the positive predictive value was 97.80% and the negative predictive value was 95.56%. Compared with the gold standard, the consistency was better (Kappa=0.934, P<0.001). Among them, the detection rate of polygenic detection was significantly different from that of strain elastography (χ2=8.766, P<0.05); the detection rate of polygenic detection was significantly different from the combination of the two. (χ2=10.686, P<0.05); the difference was statistically significant between strain elastography and the combination of the two items (χ2=33.838, P<0.05). Among the 82 malignant thyroid nodules detected by multiple genes, 74 were gene mutations and 8 were gene fusions. Among the 71 malignant thyroid nodules detected by strain elastography, 28 were scored as 4, and 42 were scored as 5. ROC curve analysis showed that the AUC values ??of polygenic detection, strain elastography, and two combined differential diagnosis of benign and malignant thyroid nodules with uncertain cytology were (0.848, 0.680, 0.968, P<0.05), respectively; the sensitivity was 82.00%, respectively , 71.00%, 96.00%; the specificity was 87.50%, 65.00%, 97.50%, respectively. Conclusion: Compared with strain elastography, the former has a higher detection rate of benign and malignant thyroid nodules with uncertain cytology, but the combination of the two is beneficial to further improve the detection rate.