Hepatocellular carcinoma (HCC) is the most common form of liver (LC) with a high mortality rate, driven by risk factors including viral hepatitis, alcoholic liver disease, and nonalcoholic steatohepatitis. The incident of HCC increases 2–4% of the worldwide population each year which would most certainly exceed one million per year by 2025. Despite advances in our knowledge, 25% of HCC tumors have actionable mutations which demands for innovative treatments strategies. In this perspective, we are providing a comprehensive summary of nanoparticles (NPs) based therapeutic approaches for HCC. We begin with an overview of HCC, concentrating on its pathogenesis, current conventional therapies, and their limitations. Then we delve into the therapeutic application of various nanoparticles (NPs) platforms for HCC, including polymeric micelles, dendrimers, liposomes, solid-lipid nanoparticles, nanostructured lipid carriers, exosomes, niosomes, mesoporous silica nanoparticles, carbon nanotubes. Special attention is given to the application of NPs in photothermal and photodynamic treatment was also investigated, with a focus on their effectiveness in targeted cancer ablation. Additionally, the review discusses recent patents and clinical studies that demonstrate the promise of NPs-based therapies in improving HCC treatment outcomes. This article underscores the potential of NPs based technologies to address the challenges faced by traditional therapies and offers insights into future directions for HCC management.