To our knowledge, ours is the first report regarding promoter hypermethylation in SFRP genes with HCC patients, and frequent methylation was confirmed in p16, GSTP1, RIZ1, SOCS1, and RUNX3. In addition, SFRP-1, -2, and -5 genes were found frequently methylated in HCC tissue. This evidence concerns the gene PRDM2 and hepatocellular carcinoma.