Dietary Polyphenols and Selected Nutraceuticals in Hepatocellular Carcinoma: Mechanistic Insights, Translational Evidence, and Clinical Prospects

Background: Hepatocellular carcinoma (HCC) develops predominantly from chronic liver injury, with diet representing a clinically actionable yet mechanistically complex modulator of hepatic carcinogenesis. Despite advances in immunotherapy, long-term survival remains poor, underscoring the need for complementary preventive and adjunctive strategies. Methods: We conducted a narrative review of epidemiological, experimental, and clinical literature on dietary patterns, polyphenols, and non-polyphenol nutraceuticals for HCC prevention and management, with a focus on underlying molecular and cellular mechanisms. Results: Dietary polyphenols and selected nutraceuticals exert pleiotropic effects on signaling pathways implicated in HCC, including NF-κB, STAT3, TGF-β/SMAD, PI3K/AKT, and Wnt/β-catenin, while modulating hepatic stellate cell activation, immune cell polarization, and microbiome-derived metabolites. Preclinical studies suggest that some compounds may enhance antitumor immunity and sensitize tumors to systemic therapies; however, clinical translation is constrained by limited bioavailability, pharmacokinetic variability, formulation heterogeneity, and a lack of high-quality trials. Conclusions: This review highlights the potential of dietary patterns and nutraceuticals in HCC prevention and as adjunctive therapies. It outlines key translational priorities, including etiologic stratification, biomarker-driven trial design, and rigorous safety evaluation.