Objective: To investigate the changes in expressions of a variety of molecular markers in thyroid papillary carcinoma (PTC) and their diagnostic values for PTC. Methods: The expressions of TPO, CK19, Galectin-3, HBME-1 and Ki-67 in the postoperative pathological specimens from 85 PTC patients and 115 patients with benign thyroid nodules (BTN) were determined by immunohistochemical staining. The diagnostic values of each molecular marker and their combination for PTC were evaluated by using receiver operating characteristic curve (ROC) and binary Logistic regression equation. Results: In PTC tissue compared with BTN tissue, the expression levels of CK19, Galectin-3, HBME-1, and Ki-67 were significantly increased, while the expression level of TPO was significantly decreased (all P<0.05). In single detection of each molecular marker, TPO showed the biggest value of the area under the ROC curve (AUC), which was 0.943; in combined detection, the combination detection of all the 5 molecular markers possessed the biggest AUC value of 0.996, but it showed no significant differences compared with any combinations that included both Galectin-3 and TPO (all P>0.05). Conclusion: The expressions of multiple molecular markers are changed in PTC, and among them, the combination detection of Galectin-3 and TPO may have a relatively high diagnostic value for PTC.