Le-Cao-Shi (LCS), a formula of Traditional Chinese Medicine (TCM), has been used as a folk medicine for protection and treatment of liver injury. However, scientific evidences on its hepatoprotective effects have not been investigated. In this study, hepatoprotective activities of LCS water extracts (LCS-W) and ethanol extracts (LCS-E) against carbon tetrachloride (CCl₄)-induced liver damage were investigated in vivo and in vitro. In vivo experiments, pretreatment of LCS-W and LCS-E to rats significantly declined the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and markedly increased the activity of superoxide dismutase (SOD) and ameliorated the level of malondialdehyde (MDA) induced by CCl₄ treatment. Especially, LCS-WM group significantly prevented the elevation of lipid peroxidation level induced by CCl_4, with the MDA level closed to that of normal group. Histopathological examinations further confirmed that LCS-W and LCS-E could protect the liver cells from CCl₄-induced damage. In addition, immunohistochemically analysis revealed that LCS-W could significantly down-regulated the hepatic protein expression of necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Correspondingly, LCS-W and LCS-E were observed to promote cell viability and decline the levels of ALT, AST, and lactate dehydrogenase (LDH) in vitro. It could be concluded that LCS can exert a protective effect against CCl₄-induced hepatotoxicity, which might be a potential therapeutic prescription for preventing or treating liver injury. Notably, LCS-W displayed better hepatoprotective activity against CCl₄-induced injury than that of LCS-E, suggesting that LCS extracted by water decoction has good development prospects. Our results contribute towards the validation of the traditional use of LCS in the treatment of liver disorders.