In order to investigate how chronic liver diseases, including liver cirrhosis and chronic hepatitis, are associate with hepatocarcinogenesis in terms of gene alteration, the methylation states of the c-myc and c-Ki-ras genes were examined in 34 liver tissues from patients with chronic liver disease without hepatocellular carcinoma (HCC), 34 non-tumor liver tissues from patients with HCC, 18 HCC tissues and 31 control liver tissues. The methylation states were analyzed by the Southern hybridization method using the restriction endonuclease isoschizomers MspI and HpaII. The CCGG sites at the second exon of the c-myc gene tended to be more extensively hypomethylated both in chronic liver disease and in non-tumor tissues than in control livers. Whereas the CCGG sites of the c-Ki-ras, and the third exon of the c-myc gene tended to be hypomethylated only in HCC tissues in comparison with other tissue groups. These results suggest that chronic liver disease may be situated between normal liver and HCC based on the state of DNA methylation and associated with the development of HCC through hypomethylation of the c-myc and/or c-Ki-ras gene.