PART1 and TLR4 are upregulated, while miR-372-3p is downregulated in HCC. PART1 promotes HCC proliferation, migration, invasion, and EMT by binding miR-372-3p, which negatively regulates TLR4. PART1-containing EVs or miR-372-3p inhibition induces M2 macrophage polarization. PART1 EVs drive HCC progression and M2 polarization via the miR-372-3p/TLR4 axis. This evidence concerns the gene TLR4 and hepatocellular carcinoma.