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Hepatocellular carcinoma (HCC) is characterized by profound lipid metabolic rewiring that supports tumor growth, therapeutic resistance, and immune evasion. Among lipid metabolic regulators, acyl-CoA synthetase long-chain family member 4 (ACSL4) has emerged as a pivotal determinant of polyunsaturated fatty acid (PUFA) activation and membrane phospholipid remodeling. Accumulating evidence reveals a functional duality of ACSL4 in HCC. On one hand, ACSL4 amplifies lipogenic transcriptional programs, enhances fatty acid oxidation-mediated energy adaptation, and cooperates with oncogenic signaling networks to promote tumor proliferation and survival, particularly under nutrient stress such as transarterial chemoembolization (TACE). On the other hand, ACSL4-driven enrichment of PUFA-containing phospholipids establishes the biochemical foundation for ferroptosis, sensitizing tumor cells to sorafenib and CD8⁺ T cell-mediated oxidative killing. This apparent paradox can be reconciled by conceptualizing ACSL4 as a context-dependent metabolic switch. Its biological output is dynamically tuned by therapeutic modality, microenvironmental redox conditions, post-transcriptional regulation (e.g., miR-23a-3p and miR-145-5p), post-translational modification (e.g., SIAH2-mediated ubiquitination), and substrate flux partitioning. Through these multilayered regulatory mechanisms, ACSL4 integrates lipid remodeling with ferroptotic sensitivity and tumor-immune interactions within the tumor microenvironment. In this mini-review, we synthesize recent mechanistic and translational findings to propose a unifying framework for ACSL4 function in HCC. Understanding ACSL4 as a metabolic switch rather than a static oncogenic factor may enable rational design of ferroptosis-enhancing and immunometabolic therapeutic strategies and support biomarker-guided precision medicine in HCC.