Hepatocellular Carcinoma (HCC) remains a formidable global health challenge, characterized by its complex etiology, aggressive progression, and high mortality rates. Metabolic reprogramming is a hallmark of cancer, and lactate, a key end-product of glycolysis, has emerged as more than just a metabolic waste product. Recent groundbreaking research has unveiled lactate’s role as a signaling molecule through a novel Post-Translational Modification (PTM) known as lactylation. Protein lactylation, particularly histone lactylation, directly links cellular metabolism to epigenetic regulation, profoundly influencing gene expression, protein function, and cellular phenotypes. In the context of HCC, an increasing body of evidence highlights the widespread and critical involvement of lactylation in various pathological processes, including tumor initiation, progression, metastasis, immune evasion, and therapeutic resistance. This comprehensive review synthesizes the current understanding of protein lactylation in HCC, detailing its intricate mechanisms, diverse functional roles in metabolic reprogramming, epigenetic regulation, immune modulation, and its significant implications as a diagnostic, prognostic, and therapeutic target. By elucidating the multifaceted contributions of lactylation, we aim to provide a deeper insight into HCC biology and pave the way for novel therapeutic strategies