Introduction: Thyroid cancers are the most common malignancy of the endocrine system. Increasing evidence has suggested potential roles for cancer susceptibility candidate 15 (CASC15) in thyroid cancer. Papillary thyroid cancer (PTC) accounts for 80% of thyroid cancer, posing a great threat to public health. The present study aims to investigate the potential roles of CASC15 in PTC. Material and methods: PTC tissues were obtained from patients diagnosed with PTC at the Second Hospital of Hebei Medical University from October 2016 to January 2018. qRT-PCR was performed to examine the mRNA levels of CASC15, Bcl-2/BAX, E-cadherin, caspase-3, and PI3K/AKT. Western blotting was applied to determine the protein levels of PI3K/AKT, CASC15, E-cadherin, BAX, Bcl-2 and caspase-3. CCK-8 assays were used to determine the viability of BCPAP and K1 cancer cells. Wound healing and transwell assays were conducted to evaluate the migration and invasion abilities of BCPAP and K1 cells. Results: The results showed that CASC15 was upregulated in thyroid cancer tissues. Moreover, CASC15 in BCPAP and K1 was decreased by CASC15 siRNA. The progression, migration and invasion of BCPAP cells were significantly decreased after transfection with CASC15 siRNA, which was consistent with that in K1 cells. Furthermore, CASC15 siRNA treatment decreased the level of Bcl-2, and PI3K/AKT, and increased the expression of E-cadherin, BAX, and caspase-3. Conclusions: Downregulated CASC15 inhibited the proliferation, migration and invasion of thyroid cancer. Therefore, CASC15 may be an oncogene in thyroid cancer and may serve as a target marker for the treatment of thyroid cancer.