Abstract Objective To explore the differential diagnosis value of CEUS quantitative analysis in the diagnosis of malignant thyroid nodules and thyroid papillary carcinoma misdiagnosed by conventional ultrasound combined with CEUS. Methods: A total of 35 nodules were selected from 35 patients who underwent conventional thyroid ultrasound and CEUS examination in the ultrasound department of our hospital from July 2018 to November 2021 and were diagnosed as malignant by preoperative combined ultrasound (C-TIRADS≥4b or CEUS with either low enhancement or rapid regression) but pathologically benign. A total of 47 patients with thyroid papillary carcinoma diagnosed by combined ultrasound at the same time and consistent with pathology were selected as control group. The characteristics of conventional ultrasound and CEUS were analyzed. The whole nodule, the central part, the marginal part and the adjacent normal thyroid parenchyma were used as areas of interest to draw time-intensity curves (TIC) for quantitative analysis, and the differences of quantitative parameters between the two groups of nodule were compared. Results The whole relative rise time (△RT) of the study group was 0.45 as the cut-off value，the sensitivity and specificity of malignant nodules were 97.9%, 85.7%, and the area under receiver operating characteristic (ROC) curve was 0.96. In the central region of the study group, △RT was used as the cut-off value of 0.55，the sensitivity and specificity of malignant nodules were 95.7%, 82.9%, and the area under ROC curve was 0.87. The sensitivity, specificity and area under ROC curve of malignant nodules were 89.4%, 77.1% and 0.89, respectively, with 0.25 as cut-off value of △RT at the peripherization of the study group. Conclusion: Quantitative analysis by CEUS has a certain value in differential diagnosis of thyroid nodules misdiagnosed by conventional ultrasound combined with qualitative diagnosis by CEUS.