This study aimed to investigate the influence of pine pollen (PP) on hepatocellular carcinoma (HCC) behavior in vitro and in vivo and explore its mechanism of action by focusing on the phosphatidylinositol 3-kinase/protein serine-threonine kinase (PI3K/AKT) signaling pathway and α-Enolase (ENO1) gene expression. This evidence concerns the gene AKT1 and hepatocellular carcinoma.