In our study, we observed that SP600125 pretreatment enhanced vitexin-reduced autophagy and inhibited vitexin-induced apoptosis in SK-Hep1 and Hepa1-6 cells, suggesting that the activation of JNK signaling plays a crucial role in the induction of apoptosis and inhibition of autophagy in liver cancer cells by vitexin treatment. Here, MAPK8 is linked to liver cancer.