Thyroid cancer is the most common endocrine malignancy, papillary thyroid carcinoma (PTC) is the main form of thyroid cancer. The long non-coding RNA (lncRNA) zinc finger antisense 1 (ZFAS1) is highly expressed in various cancer tissues and it has been shown to function as a tumor promoter in various cellular processes. However, the role of ZFAS1 in PTC is not well understood currently. Thus, this study aimed to explore the potential roles of ZFAS1 in the development and progression of PTC.PTC tissues (n=80) and noncancerous tissues were collected. Gain- and loss-of-function assays were performed to determine the effect of ZFAS1 on proliferation in K-1 and TPC-1 cells. The ZFAS1/mir-590-3P/HMGA2 aixs were analysed in PTC cell lines.We found that the expression of ZFAS1 was increased in PTC tissues and four PTC cell lines (B-CPAP, IHH-4, TPC-1, and K-1). The gain- and loss-of-function assays showed that overexpressing ZFAS1 promoted cell proliferation and inhibited cell apoptosis in PTC cells in vitro. We demonstrated that knockdown of ZFAS1 inhibits tumor growth and upregulation of ZFAS1 promotes tumor growth in vivo. Bioinformatics analysis revealed that miR-590-3p targeted the 3'-UTR of ZFAS1. The double luciferase reporter and RNA-binding protein immunoprecipitation assay demonstrated that miR-590-3p is a target of ZFAS1. Rescue experiments confirmed that miR-590-3p could reverse the effect of ZFAS1 on PTC cells. Moreover, we identified high mobility group AT-hook 2 (HMGA2) to be a downstream target of miR-590-3p and ZFAS1 which activates HMGA2 expression by sponging to miR-590-3p.High ZFAS1 expression level was associated with the progression of PTC, and ZFAS1 contributed to PTC progression via miR-590-3p/HMGA2 regulatory aixs. Therefore, ZFAS1 might be a potential therapeutic target for PTC intervention.