Abstract:  Background and purpose: Papillary thyroid cancer (PTC) comprises the most part of thyroid cancer. The research aimed to study the expression levels of cortactin and N-WASP in PTC and their relationship with clinicopathological features. Methods: Tissues from 89 cases of PTC were collected at Department of Pathology in Fudan University Shanghai Cancer Center from Jan 2012 to Dec 2017. At the same time, 89 normal thyroid tissues were selected as controls. Immunohistochemistry was used to detect cortactin and N-WASP in cancer and adjacent tissues. The expression levels of cortactin and N-WASP proteins were measured, and analysis of their relationship with clinical features was performed. Results: The positive expression rates of cortactin and N-WASP in cancer tissues were 57.30% and 59.55%, respectively, which were higher than 5.62% and 7.87% in adjacent tissues (P<0.05). The expression of cortactin was not significantly associated with age, gender and tumor size in patients with PTC (P>0.05), but it was associated with lymph node metastasis. N-WASP was associated with tumor size and lymph node metastasis (P<0.05). The positive expression rates of cortactin and N-WASP were higher in patients with lymph node metastasis (P<0.05). Conclusion: Cortactin and N-WASP were highly expressed in PTC, and were associated with lymph node metastasis of PTC. Expression levels of cortactin and N-WASP were positively correlated in PTC.