Collectively, our in vitro and in vivo experimental findings indicated that the anti-cancer effect of emodin was mediated through the suppression of intracellular cholesterol levels, and subsequently caused the attenuation of oncogenic AKT and STAT3 pathways; in addition, we confirmed that this would provide a promising therapeutic strategy for improvement of the anti-cancer efficacy of sorafenib in patients with advanced HCC. Here, AKT1 is linked to cancer.