In this study, we found that cisplatin activated the phosphorylation of ERK1/2, p38, AKT and PI3K in human hepatoma HepG2 cells and that fucoxanthin pretreatment attenuated cisplatin-induced phosphorylation of all these signaling molecules to sensitize cancer cells to apoptosis induced by cisplatin. Here, MAPK3 is linked to hepatocellular carcinoma.