The expression of reactivated Mapk10 could be observed after treatment with the demethylating reagent in silenced HCC cells, indicating that DNA hypermethylation directly mediated the inactivation of Mapk10. Furthermore, the ectopic expression of Mapk10 in silenced HCC cells dramatically inhibited the tumor cell colony formation, induced the cell apoptosis, and enhanced the chemosensitivity of HCC cells to 5-FU. Here, MAPK10 is linked to hepatocellular carcinoma.