The aim of the study was to assess the hepatoprotective potential of ethanolic extract of Andrographis paniculata (EAPE) against hepatotoxicity and liver injuries developed during cancer chemotherapy with cylophosphamide (CTX). Cyclophosphamide is a prodrug that undergoes hepatic metabolism to become the active 4-hydroxycyclophosphamide and toxic metabolites like phosphoramide mustard and acrolein. The toxic metabolites produced by CTX alter the hepatocellular membrane permeability by initiating lipid peroxidation and leading to hepatic injuries. The hepatoprotective activity of EAPE was assessed and compared with the ayurvedic preparation Liv. 52 (100 mg/kg) as well as the standard drug Silymarin (100 mg/kg). Six groups of Wistar rats (n = 6) were constituted. CTX intoxicated animals were treated with EAPE at doses of 250 mg/kg, 500 mg/kg, and 1000 mg/kg of body weight. On the 14th day, blood samples were collected and examined for liver function parameters (SGOT, SGPT, ALP, and total bilirubin content).