〔Abstract〕 Objective To investigate the mechanism of DNA methylation in papillary thyroid carcinoma, effects of the demethylated drug 5-aza-2′-deoxycytidine(5-Aza-C dR) on the expression level of death-associated protein kinase(DAPK) genes. Methods Human thyroid papillary carcinoma cell line TPC-1 and human normal thyroid cell line Nthy-ori-3 were treated with 10 μmol/L 5-Aza-CdR. Real-Time PCR and Western blot were used to detect the expression levels of DAPK, DNA methyltransferases(DNMTs)mRNA and protein before and after treatment. Results Real-Time PCR results showed that DNMTs mRNA was highly expressed in human thyroid papillary carcinoma cells compared with normal thyroid cells. After 5-Aza-CdR treatment in human thyroid papillary cancer cells, the expression level of DNMTs mRNA decreased, while that of DAPK mRNA increased, and there was significant difference(P<0.05); Western blot results showed that the expression of DNMTs protein was higher in human thyroid papillary carcinoma and DAPK protein expression was less compared with normal thyroid cells, after 5-Aza-CdR was applied for 48 h, the expression of DNMTs protein decreased and the expression of DAPK protein increased(P<0.05). Before and after administration, mRNA and protein expressions of DAPK and DNMTs in normal thyroid cells were not different. Conclusion DNA methylation plays an important role in papillary thyroid carcinoma, 5-Aza-CdR may regulate the expressions of DNMTs mRNA and protein to restore the expression of silenced DAPK gene, which may play a preventive role in thyroid papillary carcinoma.