In this study, genome-wide DNA methylation analysis using tissue samples of HCCs that were clearly derived from the precancerous background of NASH identified important tumor-related genes showing DNA hypomethylation and overexpression, such as DCAF4L2, CKLF, TRIM4, PRC1, UBE2C and TUBA1B. Genome-wide DNA methylation analysis using human clinical samples is a powerful tool for identifying tumor-related genes with significant expression alterations. Here, PRC1 is linked to metabolic dysfunction-associated steatohepatitis.