Rapamycin abrogated CENPI-induced oncogenic signaling in vitro, and CENPI silencing reduced in vivo tumor burden by 65% while suppressing the pathway and EMT.<h4>Conclusion</h4>CENPI may function as an oncogenic regulator in HCC through activation of the PI3K/AKT/mTOR-CDK2 cascade, linking cell cycle progression to EMT-associated invasiveness. This evidence concerns the gene CENPI and hepatocellular carcinoma.