The objective of the present study is to investigate the protective effect of cerium oxide nanoparticles (15mg,30mg/kg) on hepatorenal injuries induced by thioacetamide (100mg/kg ). The size of cerium oxide nanoparticles (CeO2NPs) was 50nm. We evaluated the protective effect of CeO2NPs by studying their effect on oxidative stress, inflammatory markers, and histopathological changes in the liver and kidney. CeO2NPs improved antioxidant status in liver or kidney as manifested by enhancement of reduced glutathione (GSH) and a reduction in malondialdehyde (MDA), Nitic oxide (NO), and oxidized glutathione (GSSG). Also, CeO2NPs mitigated the decrease in plasma catalase (CAT), total antioxidant capacity (TAC), and hepatorenal ATP content resulting from thioacetamide (TAA). Moreover, the treatment of rats with CeO2NPs + TAA alleviated the significant increase in plasma liver enzymes (Gamma-glutamyltransferase (GGT), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), alkaline phosphatase(ALP)), kidney function parameters (Creatinine, urea, uric acid) and inflammatory markers (C-reactive protein (CRP), tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6)). The protective effect of ZnO-NPs was affirmed by histopathological study of the liver and kidney. Our results proposed that CeO2NPs may relieve TAA-hepatorenal toxicity via their antioxidant and anti-inflammatory properties that participated in the suppression of oxidative stress.