BACKGROUND: N-Methyladenosine (mA) is a ubiquitous RNA modification with vital roles in various cancers, but little is known about its role in papillary thyroid carcinoma (PTC), a common endocrine malignancy. METHODS: In this study, an mA RNA methylation regulator-based biomarker signature was developed for the effective prediction of prognosis in patients with PTC. The gene expression profiles of mA RNA methylation regulators and the corresponding clinical information was downloaded from The Cancer Genome Atlas (TCGA). Differentially expressed mA RNA methylation regulators between tumor and normal control samples, and correlation expression levels, clinical parameters, and outcomes were evaluated. And a prognostic signature was built using a PTC cohort from TCGA. RESULTS: The expression level of HNRNPC was remarkably upregulated in tumor samples, while WTAP, RBM15, YTHDC2, YTHDC1, FTO, METTL14, METTL3, ALKBH5, KIAA1429, YTHDF1, and ZC3H13 were significantly downregulated in the cancer specimens compared with those in control samples. A three-gene prognostic signature comprising RBM15, KIAA1429, and FTO could predict overall survival in patients with PTC. In addition, the prognostic signature-based risk score was identified as an independent prognostic indicator for PTC. CONCLUSIONS: We established a robust mA RNA methylation regulator-based molecular signature for predicting prognosis in patients with PTC with high accuracy; this signature might provide important guidance for therapeutic strategies.