This study was performed to determine whether epigenetic aberrant methylation of RASSF1A might beassociated with hepatocarcinogenesis. Methylation specific-PCR was performed to identify RASSF1A promoterhypermethylation in 29 tumors and corresponding normal liver tissues. In addition, RASSF1A mRNA levelswere analyzed by quantitative real-time reverse transcription-PCR. Aberrant methylation of RASSF1A wasdetected in 25 of 29 cases (86%), with loss of RASSF1A expression evident in 8 of 22 cases (36%). No correlationbetween loss of RASSF1A mRNA and promoter hypermethylation of the RASSF1A gene was observed. Therewas a significant correlation between the methylation status of RASSF1A and hepatocellular carcinoma (HCC)patients who did not undergo chemotherapy (P = 0.03). Multivariate analysis, adjusted for tumor size, treatment,RASSF1A hypermethylation, and RASSF1A under-expression, showed RASSF1A hypermethylation to beassocaited with a better prognosis for HCC patients (HR= 0.089, 95%CI = 0.013-0.578; P = 0.012). Our findingsshowed that RASSF1A promoter hypermethylation occurs frequently, and may serve as a good prognostic factor.