Objective: To investigate the relationship between the expression of proliferation-related antigen Ki-67 and cyclooxygenase-2 (COX-2) in papillary thyroid carcinoma (PTC) tissue and the clinical pathological characteristics of patients. Methods: From From July 2020 to July 2025,58 patients with papillary thyroid carcinoma(PTC group) and 78 patients with thyroid benign nodules (benign group) were selected. The Ki-67 and COX-2 expressionwere detected by immunohistochemistry, investigated the pathological characteristics of thyroid cancer and given correlation analysis. Results: The positive rates of Ki-67 and COX-2 expression in the PTC group were 72.4% and 55.2%, which were higher than 31.0% and 25.9% in the benign group (P<0.05). With the increased of the clinical stage, the degree of differentiation and the occurrence of lymph node metastasis of thyroid cancer, the positive rate of Ki-67 and COX-2 expression were showed increased trend, and compared the difference were statistically significant (P<0.05). Pearson analysis showed that the positive rate of Ki-67 and COX-2 expression was significantly positively correlated with clinical stage and lymph node metastasis (P<0.05). Conclusion: Ki-67 and COX-2 are highly expressed in papillary thyroid carcinoma tissues, which are related to the clinical stage, degree of differentiation, and lymph node metastasis of patients. Ki-67 and COX-2 play a joint role in the occurrence and development of thyroid cancer.