The potential benefit of selenium nanoparticles (SeNPs) and vitamin E (Vit.E) that they are potent antioxidants , they were used as antioxidants against acrylamide (ACR) hepatotoxicity, ACR is found in the starchy foods that had been heated for long periods in high degrees above 120°C. So the aim of the current study was to elucidate the antihyperlipidemic and hepatoprotective effects of either SeNPs and/or Vit.E against ACR toxicity, SeNPs were characterized by SEM, EDX, TEM and they proved their spherical nanostructure. Zeta potential value was –22.9 mv with particle size with a diameter range (48.75‐67.24 nm) which proved the high stability of the used SeNPs. Seven groups of male mice were used: group I was control,group II ACR,group III was treated with SeNPs, IV group was received Vit.E and groups V,VI received ACR plus SeNPs and ACR plus Vit.E, group VII was given combination of SeNPs and Vit.E plus ACR,So,The effect of SeNPs and/or Vit.E were monitored against ACR hepatotoxicity and hyperlipidemia. ACR administration afforded significant elevation in the hepatic enzymes with severe alterations in the lipid metabolism. These findings clarified the efficacy of SeNPs and Vit.E by declining the high hepatic enzymes activities induced by ACR along with improving the lipid profile, elevation of the antioxidant enzymes (SOD,CAT and GRx), reduction of MDA level, improving histological and ultrastructutral hepatic tissues and restoration of most normal structures that were damaged in ACR group. So, SeNPs and/or Vit.E were proved to enhance the hepatic antioxidant capacities.