Tumor-associated macrophages (TAMs) play a critical role in the tumor microenvironment (TME) of hepatocellular carcinoma (HCC), primarily exhibiting M2 polarization, which promotes tumor progression. TAMs enhance HCC growth, invasion, and glycolysis, contributing to metabolic reprogramming and malignancy. Molecular networks regulating M2 to M1 polarization are potential therapeutic targets, with drugs targeting TAMs and suppressing M2 phenotypes being explored. TAMs facilitate cell-cell communication via exosomes, modulating tumor progression and therapy resistance. Non-coding RNAs influence TAM polarization in HCC. TAMs originate from circulating blood monocytes and self-replicate in HCC tissues. Their polarization is influenced by factors like FNDC5, OlT3, Wnt, ZIP9, and SLAMF6. TAMs promote HCC progression by inducing glycolysis, enhancing metastasis, and modulating immune responses. They also contribute to therapy resistance by suppressing immune responses and promoting tumor cell survival. Macrophages in HCC can be M1 or M2 polarized, with M2 macrophages supporting tumor growth and M1 macrophages inhibiting it. TAMs secrete exosomes that transfer biomolecules, affecting tumor cell behavior. Exosomal ncRNAs regulate macrophage polarization and tumor progression. DNA methylation and histone modifications influence TAM infiltration and polarization, impacting HCC progression. Anti-tumor compounds like emodin, cantharidin, and ligustilide modulate macrophage polarization, reducing M2 polarization and enhancing M1 polarization. Immunotherapy is promising but can be hindered by TAMs. Natural compounds like quercetin and synthetic drugs like sorafenib and regorafenib regulate TAM polarization and improve anti-tumor responses. Targeting TAMs offers potential therapeutic strategies for HCC.Tumor-associated macrophages (TAMs) play a critical role in the tumor microenvironment (TME) of hepatocellular carcinoma (HCC), primarily exhibiting M2 polarization, which promotes tumor progression. TAMs enhance HCC growth, invasion, and glycolysis, contributing to metabolic reprogramming and malignancy. Molecular networks regulating M2 to M1 polarization are potential therapeutic targets, with drugs targeting TAMs and suppressing M2 phenotypes being explored. TAMs facilitate cell-cell communication via exosomes, modulating tumor progression and therapy resistance. Non-coding RNAs influence TAM polarization in HCC. TAMs originate from circulating blood monocytes and self-replicate in HCC tissues. Their polarization is influenced by factors like FNDC5, OlT3, Wnt, ZIP9, and SLAMF6. TAMs promote HCC progression by inducing glycolysis, enhancing metastasis, and modulating immune responses. They also contribute to therapy resistance by suppressing immune responses and promoting tumor cell survival. Macrophages in HCC can be M1 or M2 polarized, with M2 macrophages supporting tumor growth and M1 macrophages inhibiting it. TAMs secrete exosomes that transfer biomolecules, affecting tumor cell behavior. Exosomal ncRNAs regulate macrophage polarization and tumor progression. DNA methylation and histone modifications influence TAM infiltration and polarization, impacting HCC progression. Anti-tumor compounds like emodin, cantharidin, and ligustilide modulate macrophage polarization, reducing M2 polarization and enhancing M1 polarization. Immunotherapy is promising but can be hindered by TAMs. Natural compounds like quercetin and synthetic drugs like sorafenib and regorafenib regulate TAM polarization and improve anti-tumor responses. Targeting TAMs offers potential therapeutic strategies for HCC.