Sex-determining region Y (SRY)-box 9 (SOX9) is a member of the SOX transcription factor family. Increasing evidence has reported that SOX9 plays different roles in various types of malignancies. However, the role of SOX9 in papillary thyroid cancer (PTC) is still unclear. The aim of this study was to investigate the role of SOX9 in PTC. Our results showed that SOX9 was upregulated in PTC tissues and cell lines. In addition, knockdown of SOX9 significantly inhibited PTC proliferation, colony formation, migration, and invasion, as well as epithelial-mesenchymal transition (EMT) phenotype in TPC-1 and BCPAP cells. Moreover, knockdown of SOX9 significantly inhibited the expression levels of β-catenin, cyclin D1, and c-Myc in PTC cells. In conclusion, this is the first report demonstrating that knockdown of SOX9 inhibited PTC cell proliferation, invasion, and the EMT process via suppressing Wnt/β-catenin signaling pathway. Thus, SOX9 may act as a novel molecular target for the prevention and treatment of PTC.