Abstract Most nanoparticles are metabolized and accumulated in the liver; therefore, this review, based on most data collected from PubMed.gov between 2012 and 2023 with the keywords “nanomaterials induced hepatotoxicity,” aims to elucidate the mechanism of nanoparticles leading to liver injury and propose relevant strategies. We discuss the biomedical approaches and strategies for mitigating liver injury, including 1) principle and recommendation of material selection; 2) nanoparticle surface modulation; 3) strategies inspired by virus and other biological phenomenon; and 4) drug and other possible adjunctive strategies. The optimal design of nanomaterials and therapeutic strategies to attenuate hepatotoxicity is critical for the development of nanomedicine.