Objective: The objective of this study is to investigate the protective role of Selenium Nanoparticles (SeNPs) on hepatotoxicity induced by cisplatin. This aim can be achieved by assessment of oxidative stress and antioxidants markers in liver homogenate [malondialdehyde (MDA), Superoxide dismutase (SOD), Glutathione (GSH), Glutathione peroxidase (GSH~PX) and Catalase (CAT)], serum liver function [(Alanine amino transferase (ALT), Aspartate amino transferase (AST), Total Protein (TP) and Albumin(Alb)], Complete blood count (CBC) and Histopathological examination of liver tissues. Material & Methods: Thirty adult male rats weighing 250±20g divided equally and randomly into four groups: Group І (negative control group), Group ІІ (Cisplatin group), Group ІІІ (Selenium Nanoparticles group) and Group ІV (Selenium Nanoparticles + Cisplatin). The rats of Group ІІ were be injected intraperitoneally as a single dose by cisplatin (10mg/kg), meanwhile selenium nanoparticles (2mg/kg/day) were administrated alone (Group ІІІ) or in combination with cisplatin (Group ІV). Results: Cisplatin treatment caused a significant decrease in antioxidant enzymes activities (SOD, GSH, GSH~PX and CAT), total protein and albumin levels and count of red blood cells, white blood cells and platelets while it caused elevation in MDA levels, ALT and AST activities. These biochemical parameters were confirmed by histopathological study as selenium nanoparticles improved the hepatotoxicity induced by cisplatin. Conclusion: Selenium Nanoparticles reduced cisplatin-induced hepatotoxicity, improved liver function and protected rats from liver injury.