Thyroid cancer is the most common endocrine cancer in the world and the leading cause of cancer-related death. Epigenetic changes are increasingly being related to metastasis. This work used a MethylationEPIC BeadChip (850K), RNA sequencing, and a targeted bisulfite sequencing technique to analyse whole-genome DNA methylation patterns and gene expression profiles in thyroid cancer tissue samples. The Illumina Infinium human methylation kit (850K) analysis found differentially methylated CpG sites (DMPs) and differentially methylated CpG regions (DMRs) across almost the whole genome with great resolution and depth. Gene ontology and KEGG pathway analysis found that DMR-associated genes belonged to a variety of domain-specific ontologies, including cell adhesion, molecule binding, and proliferation. The researchers discovered 1627 differentially expressed genes, 1174 of which were up-regulated and 453 of which were down-regulated, using RNA-Seq. The targeted bisulfite sequencing experiment demonstrated that methylation levels of CHST2, DPP4, DUSP6, ITGA2, SLC1A5, TIAM1, TNIK, and ABTB2 were considerably reduced in thyroid cancer patients compared to controls, although GALNTL6, HTR7, SPOCD1, and GRM5 were significantly higher. Our findings show that whole-genome DNA methylation patterns and gene expression levels in thyroid cancer provide fresh insight on thyroid cancer carcinogenesis.