Objective To study on preoperative diagnosis of papillary thyroid carcinoma (PTC) with Bethesda Ⅴ thyroid nodules retrospectively and to explore the differences of clinical parameters between Bethesda Ⅴ and Ⅵ thyroid nodules. Methods The clinical data of 430 patients were analyzed. Results Univariate analysis showed that there were significant differences of Bethesda Ⅴ nodules in nodule boundary, tumor size and echo between PTC group of 159 cases and benign group of 20 cases (P<0.05). It was shown from multivariate analysis that nodule boundary, tumor size and echo were risk factors for malignant diagnosis of BethesdaⅤnodule. The differences were present significantly in TI-RADS grade, aspect ratio and echo between Bethesda ⅤPTC group of 159 case and Bethesda Ⅵ thyroid nodule group of 251 cases (P<0.05). Further multivariate analysis showed that TI-RADS grade, aspect ratio, relation of nodule with capsule, thyroid peroxidase antibody level and echo were the risk factors for the diagnosis of PTC. Conclusions Bethesda Ⅴ nodules with higher grade of TI-RADS are malignant more possibly and those with lower grade of TI-RADS need to be evaluated such as thyroid nodules sizes, relation of nodules with capsule and thyroid peroxidase antibody level.