Although chemotherapeutic drugs are widely applied for clinic tumor treatment,severe toxicity restricts their therapeutic efficacy.In the study,we reported a novel form of selenium,selenium nanoparticles(Nano Se)which have significant lower toxicity and acceptable bioavailability.We investigated Nano Se as chemotherapy preventive agent to protect against toxicities of anticancer drug irinotecan and synergistically enhance the anti-tumor treatment effect in tumor-bearing mice in vivo.The underlying mechanisms were also investigated.Nano Se at a dose of 4mg/kg/day significantly alleviated the weight loss and hematological adverse effects,as well as elevated transaminase and histopathological alterations of liver induced by irinotecan(60 mg/kg)treatment.Nano Se alone treatment did not induce any toxic manifestations.The combination of Nano Se and irinotecan dramatically inhibited tumor growth and significantly induced apoptosis of tumor cells in HCT-8 cells xenografted tumor.Tumor inhibition rate was about 17.2%,48.6%and 62.1%for Nano Se,irinotecan and the combination of Nano Se and irinotecan,respectively.The beneficial effects of Nano Se for tumor therapy were mainly ascribed to selectively regulating Nrf2-Prx1 pathway in tumor tissues and normal tissues.Our study results suggest Nano Se is a promising selenium species with potential application in cancer treatment.