Triclosan (TCS) is a widely used antimicrobial agent that is used worldwide since 1972. It can be found in various hygiene, medical and consumer products. Due to its widespread use, TCS has increasingly been a public health concern. The present study aimed to assess the histopathological potential and DNA damage induction of TCS treatment in liver tissues in male albino mice and to evaluate the protector role of vitamin E (Vit E) against TCS toxicity. TCS (15 mg/kg) was injected intraperitoneal for 2 consecutive days. Other group was orally administrated with Vit E (50 mg/kg) just before TCS injection. Mice were sacrificed after 24hr from the last treatment. Liver tissues were used for histopathological and molecular evaluations (Comet assay). In the present study, TCS treatment causes damage of liver tissues represented by congested central vein and hepatoportal vessels, mononuclear cells infiltration in portal area and slight hepatic degeneration with local area of leucocytic infiltration. Moreover, the results show a significant increase in tail length, % DNA in tail and tail moment for TCS group in comparison with the negative control group in comet assay. On the other hand, Vit E pretreatment was able to protect liver tissue from TCS toxic effect. In conclusion, the present study reports the toxic potential of TCS treatment and the ameliorative effect of Vit E pre-oral administration as a result of its antioxidant property to scavenge free radicals.