Abstract: Objective: To study the relationship between methylation of CpG islands in the E-cadherin (E-cad) promoter and clinicopathologic features of hepatocellular carcinoma (HCC). Methods: The methylation status of CpG islands was studied using Methylation-Specific PCR for the E-cad gene in tumor tissues and corresponding normal tissue from 53 HCC patients and 15 cases with paraneoplastic tissues of hepatic sponginess hemangioma. Results: The frequency of methylation of CpG islands in the E-cad gene was significantly higher among the HCC tumor tissues as compared to the corresponding normal tissues (P=0.007, P<0.01), and the paraneoplastic liver tissues (P=0.006, P<0.01). The frequency of methylation of CpG islands in the E-cad gene was significantly higher in stage Ⅲ~Ⅳ cases as compared to the stage Ⅰ~Ⅱ cases (P=0.037, P<0.05), and in well-encapsulated tumors compared to poorly-encapsulated tumors (P=0.043, P<0.05), and in tumor tissues positive for Hepatitis B virus (HBV) compared to tumors negative for HBV (P=0.024, P<0.05). Differences in the frequency of methylation of CpG islands in the E-cad gene between large tumors (diameter>5cm) and small tumors (diameter≤5cm) and between tumors with a single nodule and multiple nodules were not statistically significant. Conclusion: Methylation of CpG islands for the E-cadherin gene maybe involved in the pathogenesis of HCC.