Introduction Hexavalent chromium Cr (VI) is a strong oxidizing toxic agent. It penetrates cell membrane and quickly reduced with production of reactive intermediates and reactive oxygen species that react with the DNA causing anomalies in the cell structure. Vitamin E (vit. E) is a lipid soluble antioxidant preventing damage to membranes also selenium (Se) is an essential micronutrient with an antioxidant activity. Aim of the present study was to evaluate the hepatotoxicity, nephrotoxicity, and genotoxicity induced by acute Cr (VI) toxicity. Also, to evaluate and compare the possible protective role of vit. E and Se against that toxicity. Methodology: This study was carried out on 60 adult male albino rats divided into 10 rats of six groups, negative control group, selenium control group (0.5 mg/kg IP for 5 consecutive days), vitamin E control group (125 mg/kg orally for 14 days), Cr (VI) group (10 mg/kg single dose IP), Cr (VI) + Selenium group and hexavalent chromium + Vitamin E group. Liver and kidney function tests, total protein, oxidative stress, antioxidant markers and genotoxic analysis were done to all groups. Result: Acute Cr(VI) toxicity resulted in increased levels of the studied liver, kidney , oxidative stress markers, all forms of chromosomal aberrations and elevation of DNA damage. It decreased levels of total protein and antioxidant markers. Treatment with Se or vit. E resulted in improvement in all these effects. Conclusion& recommendation: Cr (VI) is a hepatotoxic, nephrotoxic, and genotoxic. Se or vit. E has the ability for reduction of these deleterious effects. So it is recommended to do regular medical examination of workers exposed to hexavalent chromium for early detection of any health problem and afford dietary supplementation with vitamin E and selenium.