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Various types of research on the biological activities and chemical components of Asteraceae were performed, but few kinds of studies on in vivo bioactivity ofHertiacheirifoliawere focused. The objective of the current investigation was to evaluate the potency of H. cheirifoliabutanol extract (BEHC) alone and in combination withselenium (Se) to protect rats' kidneys from carbon tetrachloride (CCl4)-induced damage. The plant extract was given orally at doses of 100 and 400 mg/kg, then biochemical and oxidative stress parameters were investigated after two weeks experimental period. Results showed that BEHC contained the highest amounts of polyphenols and administration of CCl4 induced kidney damage by increasing significantly the levels of urea and malondialdehyde and decreasing GSH, CAT, and SOD levels in renal tissues. Moreover, CCl4 provokes histopathological kidney lesions. However, pretreatment with BEHC and Se has protected rats against CCl4 toxicity, significantly reduced oxidative stress, improved renal histological aspects, and ameliorated the biochemical parameters. Due to its potent natural antioxidant activity, the n-butanol extract of H. cheirifolia can reduce nephrotoxicity when combined with selenium.