The present study was aimed to evaluate the radioprotective efficacy of lycopene, a naturally occurring dietary carotenoid on whole body radiation-induced cellular damage in the liver of Swiss albino mice. The first phase of the study was carried out to fix the effective concentration of lycopene by performing a 30 days survival studies using different graded doses (10, 20, 40 and 80mg/kg body weight) of lycopene administered orally to mice via intragastric intubations for seven consecutive days prior to exposure of whole body radiation (10Gy). Based on the results of survival studies, the effective dose of lycopene was fixed which was then administered to mice orally via intragastric intubations for 7 consecutive days prior to exposure of whole body radiation (4Gy) to evaluate its radioprotective efficacy by performing various biochemical estimations, comet assay, DNA fragmentation assay and histopathological alterations in the liver of Swiss albino mice. The results indicated that radiation-induced decrease in the levels of endogenous antioxidant enzymes and increase in lipid peroxidative index, DNA damage and comet assays were altered by pre-administration with the effective dose of lycopene (20mg/kg body weight) which restored the antioxidant status to near normal and decreased the levels of lipid peroxidative index, DNA damage and comet assays. These results were further confirmed by histopathological examinations, which indicated that pre-administration with the effective dose of lycopene reduced the hepatic damage induced by radiation. Thus the current study shows lycopene to be an effective radioprotector against radiation-induced damage in the liver of mice.