Objective:To analyze the metabolic mechanism of papillary thyroid cancer(PTC) in normal and Hashimoto′s thyroiditis(HT) background, and to explore the relationship between HT and PTC.Methods:This study included a matched sample set collected from Tianjin Medical University General Hospital between January 2018 and January 2019, consisting of PTC and paracancular tissue from 31 cases with coexisting HT(HT group), and 30 cases without(NC group), all confirmed pathologically following thyroidectomy. The ultra-high performance liquid chromatography combined with mixed four-stage poles time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to acquire data from the samples. Metabolite differences between the two groups were compared, aiming to identify distinct metabolic mechanisms of PTC under different backgrounds. Metabolic pathway analysis was conducted using Metabo-Analyst 5.0 to explore relevant metabolic pathways.Results:The HT group and NC group shared 7 common differentially expressed metabolites, including arginine, glutamic acid, cysteine, citric acid, malic acid, uracil, and taurine. Logistic regression model combined with receiver operating characteristic(ROC) analysis of these 7 biomarkers yielded excellent discriminatory capacity for PTC(area under ROC curve of HT group and NC group were 0.867 and 0.973, respectively). The common metabolic pathways were taurine and hypotaurine metabolism, arginine biosynthesis, alanine, aspartic acid and glutamic acid metabolism, arginine and proline metabolism, and glutamine and glutamic acid metabolism. The specific metabolic pathways in HT group were aminoacyl tRNA biosynthesis, glycine, serine, and threonine metabolism.Conclusion:The metabolic profiles of thyroid cancer exhibit significant differences between cases with normal backgrounds and those with HT. The specific pathways for PTC and HT are aminoacyl tRNA biosynthesis and the metabolism of glycine, serine, and threonine.