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Recently, the fundamental roles of microRNAs (miRNAs) in the progression and development of diseases have been shown in several studies. In the liver 70% of all expressed miRNAs is miR-122; therefore it is measured as a liver-specific miRNA. The aim of this work was to evaluate the hepatoprotective and radioprotective effect of orally administrated naringin and silymarin pretreatment in CCl4-intoxicated and γ-irradiated rats, also to study the change of gene expression of microRNA and change of IL-6 levels to find powerful and reliable tools that can be used as a biomarker for the diagnosis of hepatotoxicity and radiation exposure for monitoring and treatment. This study revealed that pre-treatment of rats with naringin orally (80 mg/kg b,w) significantly restored the levels of superoxide dismutase (SOD), lipid peroxidation (MDA) and reduced glutathione (GSH) in rats injected with 1 ml/kg b.wi.p CCl4 and in rats exposed to 7 Gray single one shot dose of γ radiations. The combination between naringin and silymarin resulted in significant reduction in IL-6 level in hepatotoxic rats. MicroRNA-122 expression changes in hepatotoxicity and radiation emphasize the great value of miRNA signatures as hepatotoxicity and radiation biomarker.