Selenium nanoparticles have received wide attention because of their importance in nutrition compared to other forms of selenium used in food fortification. Within recent study, selenium nanoparticles (SeNPs) were prepared, characterized and evaluated in albino rats to identify their hepatic protective effect against cyclophosphamide-induced hepatotoxicity. Fifty white albino rats were divided randomly into five groups. Group I was used as a negative control, group II was administrated daily dose of CP (5 mg/kg body weight/8 weeks) orally by gavage, group III were administrated SeNPs orally at a dose of (2 mg/kg body weight / 12 weeks) three times weekly. Group IV was administrated CP at a dose of (5 mg/kg body weight/8 weeks) daily orally then administrated SeNPs orally at a dose of (2 mg/kg body weight / 4 weeks) three times weekly. Group V(protected group) was administrated SeNPs orally at a dose of (2 mg/kg body weight/4 weeks) three times weekly, then administrated daily dose of CP (5 mg/kg body weight/8 weeks) orally with continuous administration of SeNPs till the end. Based on results obtained, CP administration in group II showed significant increase in serum liver enzymes activity(AST, ALT, and ALP), which was followed by a substantial significant decrease in serum albumin conc. and tissue antioxidants (GPx, SOD, and CAT) activity, with significant increase in cytokine levels (IL6,IL1β). Such biochemical changes were significantly improved by Nano-Se treatment, particularly in the protected rats. The current study found that Nano-Se reduces oxidative stress in liver tissue caused by CP administration.