Papillary thyroid cancer (PTC) is a frequent thyroid malignancy. With the significant regulatory role in tumor progression, more attention has been employed to investigate mechanism of long noncoding RNAs (lncRNAs) in progression of PTC. We prospectively explored the mechanism whereby lncRNA SET-binding factor 2-antisense RNA1 (SBF2-AS1) is implicated in pathogenesis of PTC. First, differentially expressed SBF2-AS1 between PTC and normal adjacent thyroid tissues was determined, and result indicated a higher SBF2-AS1 expression in PTC tissues than adjacent normal tissues. Moreover, highly SBF2-AS1 expression predicted a poor prognosis in PTC patients. Second, SBF2-AS1 overexpression promoted cell viability and cycle of PTC, while inhibited cell apoptosis. However, SBF2-AS1 downregulation reduced viability and cycle, while promoted cell apoptosis. Moreover, SBF2-AS1 could bind with miR-431-5p and showed negative correlation with miR-431-5p in PTC patients. Furthermore, miR-431-5p bind with cyclin-dependent kinase (CDK) 14 and showed negative correlation with CDK14 in PTC patients. Finally, overexpression of CDK14 counteracted with the inhibitory role of SBF2-AS1 downregulation on cell viability, cycle, and apoptosis of PTC. In conclusion, SBF2-AS1 exhibited oncogenic property in PTC, and knockdown of SBF2-AS1 could be a therapeutic strategy for PTC. © 2020 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia on behalf of Kaohsiung Medical University.