Objective To study the expression of O6-methylguanine-DNA methyltransferase (MGMT) and its clinicopathological significance in thyroid cancer.Methods Immunohistochemistry was used to determine the expression of MGMT in 61 thyroid cancer tissues, 21 thyroid adenomas, 15 Hashimoto's thyroiditis, 8 nodular goiter, and 12 peri-tumor tissues. Results There was statistic difference in the expression of MGMT between the normal tissues and thyroid cancers (P＜0.05). Expression of MGMT increased from the normal tissue (16.67%, 10/12), nodular goiter (25.00%, 2/8), Hashimoto's thyroiditis (60.00%, 9/15), and thyroid adenoma (52.38%, 11/21)to thyroid cancer (60.66%, 38/61). Expression of MGMT in papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) had significant difference (P＜0.05), and the expression level of MGMT decreased with the malignancy of thyroid cancer, such as in PTC (72.22%, 26/36), and FTC (50.00%, 8/16). There was no statistic difference in MGMT expression in sex, age, and nationality (P＞0.05).Conclusion High expression of MGMT might be related to the malignancy of thyroid cancer, which may be one of the diagnosis indexes for thyroid cancer. It will be a common clinical index in diagnosingthyroid cancer since there is no difference in MGMT expression among sexes, ages, and nationalities.