IntroductionThe incidence of thyroid cancer is increasing and histological test by itself cannot differentiate thyroid cancer from some benign nodules. Our immediate goal is to meta-analysis and determines the impact of promoter methylation of eight selected candidate TSGs on thyroid cancer and to identify the most important molecules in this carcinogenesis pathway.Methods and analysis\u00a0We will include observational studies evaluating the promoter methylation in patients with thyroid cancer. A comprehensive search was performed using PubMed, Scopus, and ISI Web of Knowledge databases, and eligible studies were included. The methodological quality of the included studies was evaluated according to the Newcastle Ottawa scale table and pooled odds ratios (ORs); 95% confidence intervals (CIs) were used to estimate the strength of the associations with Stata 12.0 software. Egger\u2019s and Begg\u2019s tests were applied to detect publication bias, in addition to the \u201cmetatrim\u201d method.Ethics and disseminationNo ethical issues are predicted. These findings will be published in a peer-reviewed journal and presented at national and international conferences.Registration numberThis systematic review protocol is registered in the PROSPERO International Prospective Register of Systematic Reviews, registration number (CRD42016033484).Strengths and limitations of this studyThis systematic review, for the first time, will conduct to evaluate the prognostic and diagnostic accuracy of DNA methylation in patients with thyroid cancer using comprehensive search of several databases. The study screening, data extraction, and risk of bias assessment of the current study will be conducted by two researchers independently. We expect some potential heterogeneities between previous studies, including stage, and histological grade in patient samples.