Introduction: Now a day__ampersandsignrsquo;s liver disease is a worldwide problem. Modern synthetic drugs used in the treatment of liver diseases are sometimes inadequate and can cause serious side effects. Objective: This current investigation aims to evaluate the ethanol and aqueous extracts of leaves of Chromolaena odorata (L.) R. M. King __ampersandsignamp; H. Rob. (Asteraceae) was investigated against carbon tetrachloride and rifampicin-induced hepatic damage. The plant of Chromolaena odorata is a perennial herb and distributed throughout the region of India, Mexico and Asia. In traditionally this plant is used in the treatment of coughs, colds, and skin diseases. Based on the present study, an effort has been made to establish the scientific validity of the hepatoprotective activity against ccl4 and rifampicin-induced hepatotoxicity. Methods: To evaluate the hepatoprotective activity by various inducing agents like carbon tetrachloride at the rate of 1 ml/kg and rifampicin 1mg/kg produced liver damage in rats. Results: The results are manifested by the significant (P__ampersandsignlt;0.005) rise in serum levels of Serum oxaloacetate transaminase(SGOT), Serum glutamate pyruvate transaminase(SGPT), alkaline phosphatase (ALP), Total protein Totalbilirubin and Directbilirubin compared to respective control values. Histopathological observation also revealed that pretreatment with Chromolaena odorata protected the animals from carbon tetrachloride and rifampicin induced liver damage. Conclusion: From the present work we can strongly conclude that plant of Chromolaena odorata is biologically huge potential value. The preliminary chemical test of the samples revealed the presences of high-value phenolic compounds as the major content in the plant of Chromolaena odorata.