This study isolates extracellular vesicles and particles (EVPs) from hepatocellular carcinoma (HCC) cells. Biophysical and proteomic analyses demonstrate that sEVs and exomeres are distinctive entities. GALNS and MAN2B1 are identified as potential EM markers. HCC-derived EMs promote oncogenesis via several mechanisms, including PI3K/AKT/mTOR activation, cell cycle progression, and lipidomic dysregulation.