Abstract： Objective To investigate the suppressing effect on hepatocellular carcinoma cell proliferation by up-regulating histone acetylizad level with a selective inhibitar of HDACs-Valproate acid sodium(VPA).And the mechanism which involved was clarified by detecting the protein and mRNA expressions of Cyclin A、Cyclin D1、Cyclin E、P21Walf/cipl.Methods HepG2 cells wero cultured with 0.75-4.0 mmol/L valproic acid(VPA)for 24,48,72,96hrs in vitro.The inhibition rate was studied by MTT assay:clone forming inhibit rate was tested by clonay assay;cell cycle was analyzed by flow cytometry with PI assay,and the protein and mRNA expressions of Cyclin A、Cydin D1、Cychn E、P21Waf/cip1 of HepG2 cells after 1.5.3.0 mmol/L VPA treated wero analyzed by indirect immunofluorescence technique and RT-PCR respectively.Results The inhibition rate of experimental group increased significantly(P＜0.001)and a dose and acting time dependence was found.Clones in experimental groups decreased more than in control group.As for cell cycle,the percentage of G1,S,M phrase in control group remained the same.Compared with control group,0.75 and 4.0 mmol/L VPA induced a significant arrest in G1 phrase(P＜0.001)and a total of 55.4%～82.8% G1 phrase of cells which cultured with VPA.Cychn A.Cyclin D1 were down-regulated both at mRNA and protein level(P＜0.001)while P21Waf/cip1 was up-regulated both at mRNA and protein level.Conversely,neither mRNA nor protein expression of Cyclin E showed any difierence between experimental and control group(P＞0.05).Conclusion Up-regulating histone acetylizad level can inhibit hepatocellular carcinoma cell proliferation,inhibit cell clone formation,induce cell cycle arrest in G1 phrase.VPA.as a Ⅰ class of histone deacetylase inhibitor can be used as an option in the treatment of hepetoma.The mechanism includes upregulating P21Waf/cip1 mRNA and protein expression,down-regulating Cyclin A,Cyclin D1 mRNA and protein expression.