Abstract: Objective To investigate promoter methylation status,mRNA expression of 14-3-3σ gene and their relationship in hepatocellular carcinoma(HCC). Methods The methylation status of the 14-3-3σ gene in tissues were detected with methylation-specific PCR.The 14-3-3σ mRNA expression was examined by real-time PCR. Results Hypermethylation of CpG islands of the 14-3-3σ gene was detected in 93.2%(41/44) of the HCC tissues,56.1%(23/41)of cirrhotic tissues and 6.8%(3/41) of cancer-adjacent tissues,no significant difference between different clinical pathological features, such as gendre, differentiation and HBV infection status. mRNA expression of 14-3-3σ in tissues without methylated product approximated to the normal level, whereas, that in 58/ 64 (90. 6 %) of samples with methylated product were lower than the detection limit, 10. 4 % were lower than the normal level. The expression and methylation of 14-3-3σwere negatively correlated ( P < 0. 05) . Conclusion 　These result s indicate that hypermethylation plays a causal role in inactivation of the 14-3-3σgene in HCC. Hypermethylation and the resulting loss of expression of the 14-3-3σgene corresponds to one of the most common abnormalities reported to date in HCC, suggesting their crucial role in the development of HCC.