Our results suggest that higher methylation of CDC5L-cg05671347, MERTK-cg08279316, RHOA-cg05657651 and YBX1-cg16306148, and lower methylation of BCR-cg25410636, DFFA-cg20696875, SCUBE2-cg19000089 and TP63-cg06520450, were associated with better OS in HCC patients, with the exception of MERTK-cg08279316, they were independent prognostic factors for OS in HCC patients. This evidence concerns the gene DFFA and hepatocellular carcinoma.