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Objective: To study the methylation state of DAPK, THBS1, RIZ1 and MGMT genes in hepatocellular carcinoma (HCC). Methods: The technique of methylation-specific PCR (MSP) was adopted to investigate the promoter hypermethylation of DAPK, THBS1, RIZ1 and MGMT genes in 40 paired HCC and non-tumor liver tissues samples and 2 normal liver tissues. The relationship between the frequency of hypermethylation of the genes and clinical data was analyzed. Results: The phenomenon of genes methylation was absent in patients with normal liver. In patients with HCC, the frequency of hypermethylation in DAPK, THBS1, RIZ1 and MGMT were 77.5% (31/40), 37.5% (14/40), 30% (12/40) and 15% (6/40), respectively. In the paired non-tumor liver tissues, the frequency of hypermethylation in DAPK, THBS1, RIZ1 and MGMT were detected in 77.5% (31/40), 27.5% (11/40), 5% (2/40) and 5% (2/40), respectively. 87.5% (35/40) of HCCs and 80% (32/40) of the non-tumor liver tissues had hypermethylation of at least one gene. The samples of one gene, two genes, three genes and four genes methylation in tumor tissues was 16 (40%), 11 (27.5%), 7 (17.5%) and 1 (2.5%) in tumor tissues. None of the patients had three or four genes methylation in the non-tumor tissues. There were 18 (45%) samples of one genes methylation and 14 (35%) samples of two genes methylations in the non-tumor tissues. Hypermethylation of RIZ1 was more frequent in HCC than in non-tumor liver tissues (X~2=8.658, P <0.05). And the statistical association of RIZ1 methylation between HCC and non-tumor tussues was found ( K=0.219, P<0.05). No statistical significance was
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