Background: Drugs for the treatment of liver diseases are scarce and not effective enough. Some species of the genus Cirsium possess hepatoprotective activity. There are no studies on the hepatoprotective effects of nonpolar extracts from inflorescences of thistles Cirsium vulgare and Cirsium ehrenbergii, and there are few reports on their chemical composition. Objective: The aim is to obtain the hexane extract from inflorescences of both thistles and to identify preliminarily their main chemical component, and to evaluate the hepatoprotective properties of the extracts. Materials and Methods: Hexane extracts were obtained using a Soxhlet apparatus. The chemical composition was analyzed using infrared spectra and gas chromatography-mass spectrometry. Two doses (250 and 500 mg/kg, p.o.) of both extracts were administered to assess their hepatoprotective effect on acute carbon tetrachloride (TC)-induced liver damage in rats using biochemical markers of necrosis, cholestasis, functionality, oxidative stress, and histological analysis. Results: Extracts were shown to have a very similar chemical profile. Their major constituent seems to be lupeol acetate. The two doses of both extracts demonstrated comparable hepatoprotective properties because they significantly diminished all the liver injury indicators (P < 0.05) and were corroborated using histopathology. Conclusion: This is the first study on the hepatoprotective effects of nonpolar extracts from inflorescences of thistles C. vulgare and C. ehrenbergii. Hexane extracts administration totally prevented the acute TC-induced liver damage. The preliminary chemical analysis strongly suggests the lupeol acetate as their major constituent. Lupeol and its derivatives have been previously reported as antiinflammatory and hepatoprotective agents.