Objective To determine the possible differences in DNA methylation of benign and malignant thyroid tumors and its role in tumorgenesis and tumor progression. Methods Infinium human methylation 450 bead chip platform was utilized to screen the whole-genome of benign and malignant thyroid tumor tissues surgically removed from a patient for the determination of their DNA methylation levels. The genes with significant differences in methylation were analyzed for their functional pathways with bioinformatics. Results There were significant differences in DNA methylation between benign and malignant thyroid tumor. The inflammation-related pathways, such as T cell, Jak-STAT and cytokine-cytokine receptor signaling pathways involved in the biological process of tumorgenesis and tumor progression. Conclusions The differences in DNA methylation between benign and malignant reveal a close relationship between inflammation and tumorgenesis and tumor progression and provide a novel method for investigation of thyroid cancer development and target drug discovery.