Exposure to metallic nanoparticles (NPs) can result in inadvertent NP accumulation in body tissues. While their subsequent cellular interactions can lead to unintended consequences and are generally regarded as detrimental for health, they can on occasion mediate biologically beneficial effects. Among NPs, cerium oxide nanoparticles (CeO2 NP) possess strong antioxidant properties and have shown to alleviate certain pathological conditions. Herein, we show that the presence of cubic 25 nm CeO2 NP was able to reduce TGF-β-mediated activation in the cultured hepatic stellate cell line LX2 by reducing oxidative stress levels and TGF-β-mediated signalling. These cells displayed reduced classical liver fibrosis phenotypes, such as diminished fibrogenesis, altered matrix degradation, decreased cell motility, modified contractability and potentially lowered autophagy. These findings demonstrate that CeO2 NP may be able to ameliorate hepatic fibrosis and suggest a possible therapeutic pathway for an otherwise difficult-to-treat condition.