Objective　DNA　Methylation　of　the　tumour　suppressor　gene　leading　to　gene　silencing　plays　an　important　role　in　thyroid　tumour　development.　The　purpose　was　to　determine　the　DNA　methylation　status　of　phosphatase　and　tensin　homolog　(PTEN)　and　death-associated　protein　kinase　(DAPK)　in　patients　with　thyroid　nodules　and　to　explore　whether　they　can　be　used　as　molecular　diagnostic　tools　to　differentiate　benign　and　malignant　thyroid　nodules.　Design,　patients　and　measurements　Thyroid　tissue　and　blood　samples　were　obtained　from　normal　healthy　individuals　(controls)　and　patients　suffering　from　clinically　diagnosed　thyroid　nodular　disease　[papillary　thyroid　carcinoma　(PTC),　adenoma　and　nodular　goitre].　DNA　methylation　level,　mRNA　expression　and　protein　expression　of　PTEN　and　DAPK　in　the　thyroid　tissues　and　peripheral　blood　were　detected　using　methylation-specific　PCR,　semi-quantitative　reverse　transcription　PCR　and　Western　blot,　respectively.　Diagnostic　sensitivity,　specific　and　accuracy　of　detection　were　evaluated　between　blood　and　thyroid　tissue.　Results　There　was　a　significant　increase　in　the　level　of　DNA　methylation　of　PTEN　and　DAPK　in　PTC　(P　＜　.05)　compared　with　controls　and　other　types　of　thyroid　nodules.　Levels　of　the　mRNA　of　both　PTEN　and　DAPK　were　lower　in　PTC　in　both　peripheral　blood　and　tissue　samples　compared　with　controls,　while　there　was　concomitant　decrease　of　both　PTEN　and　DAPK　protein　expression　in　PTC　tissues　(P　＜　.05).　There　was　no　significant　difference　in　diagnostic　specificity,　sensitivity　and　accuracy　between　blood　sample　and　thyroid　tissues.　Conclusions　Hypermethylated　status　of　both　PTEN　and　DAPK　in　peripheral　blood　and　tissue　samples　can　be　useful　biomarkers　for　clinical　diagnosis　and,　distinguishing　of　benign　and　malignant　thyroid　nodules.