ObjectiveTo screen prognosis prediction targets related to progression free survival (PFS) for patients with papillary thyroid cancer (PTC) based on the RNA binding proteins (RBPs) gene set. MethodsThe clinicopathologic data of patients with PTC were obtained from UCSC Xena database and the cancer tissues and paired tissue adjacent to cancer (a distance >2.0 cm) of the patients with PTC underwent thyroid surgery were obtained from the First Affiliated Hospital of Zhengzhou University. The differentially expressed RBPs genes between the cancer and normal tissues were determined from the comprehensive analysis of multiple public data sets, and the RBPs genes related to PFS were determined by univariate and multivariate Cox analyses. Western blot method was used to verify the protein expression of RBPs gene in the clinical cases. The RBPs genes with prognostic value and in combination with clinicopathologic parameters were use to establish a nomogram associated with prognostic prediction. Results① A total of 424 patients with PTC were included from the UCSC Xena database and 30 patients with PTC were collected from the First Affiliated Hospital of Zhengzhou University. ② Seven down-regulated RBPs genes (ARHGEF28, IGF2BP2, KHDRBS2, MVP, PPARGC1A, SMAD9, TDRD9) and 3 up-regulated RBPs genes (ZFP36, ZFP36L2, ZMAT3) were identified in PTC. ③ The RBPs gene ZFP36 associated with PFS was screened by multivariate Cox analysis. ④ The Western blot result showed that the expression of ZFP36 protein was basically consistent with its gene expression. ⑤ The areas under the receiver operating characteristics curve of nomogram constructed in combination the clinicopathologic features related to PFS (M stage, T stage) with ZFP36 in predicting 1, 3, and 5-year PFS rates were 0.80 [95%CI (0.69, 0.91)], 0.72 [95%CI (0.62, 0.81)], and 0.64 [95%CI (0.50, 0.77)], respectively. The consistency index of nomogram was 0.724 [95%CI (0.685, 0.763)], and the calibration curve of the 3-year PFS probability was very close to the ideal diagonal. ConclusionAccording to the preliminary research results of database and clinical case data, RBPs ZFP36 might be a potential prognostic target for patients with PTC.