〔Abstract〕 Macropinocytosis (MP) is an actin-dependent process by which cells internalize large volumes of extracellular fluid. This engulfed material is subsequently digested and degraded within lysosomes, providing essential nutrients that enable cell survival and growth under hypoxic and nutrient-scarce microenvironments. In the pathogenesis of hepatocellular carcinoma (HCC), sustained liver inflammation plays a critical role. Chronic liver inflammation not only creates favorable conditions for MP activation but also triggers relevant signaling pathways, thereby establishing a persistent positive feedback loop. This review aims to systematically elucidate the mechanistic basis of MP, summarize recent advances in its regulation via relevant signaling pathways during HCC progression, and discuss the potential value of targeting MP as a therapeutic strategy for HCC, thereby providing insights for future clinical research.