Background: To evaluate the promoter methylation status of RECK gene and mRNA expression in patients with hepatocellular carcinoma (HCC).Methods: We analyzed RECK methylation by MSP, and RECK mRNA by real-time PCR in 74 HCC.The liver cell lines (7721, Chang and Hep-G2) were treated with 5-Aza-CdR and TSA.Results: RECK mRNA were lower in HCC tissues (Mean-△ct =-3.29) than that in Non-Hcc tissues (Mean △ct =-2.42).Expression of RECK was elevated in only 24 (32.43%) of the 74 HCC patients but decreased (-△△Ct<0) in 50 (67.57%) of the patients.RECK promoter was hypermethylated in 55.4% (41/74) of HCCs, and in only 17.6% (13/74) of Non-Hcc samples.RECK mRNA were lower in HCC patients with hypermethylation (△MI>=0.5) (Mean -△△Ct =-1.75) than those with demethylation (△MI<0.5) (Mean-△△Ct =0.05), and there is a decreased tendency for RECK mRNA in HCC patients with promoter hypermethylation (p =0.002).There was a significantly correlation found between RECK mRNA and poor survival after surgery.After treated by 5-Aza-CdR and TSA, we found that RECK mRNA induced different changes in 7721, Chang and Hep-G2 cells.And RECK demethylation also induced by epigenetic inhibitors.Conclusion: The results suggested that the hypermethylation may lead to promoter si lencing of RECK mRNA and associated with poor survival in HCC.