ABSTRACT This study was designed to evaluate the hepatoprotective effect of alcoholic and n-hexane extracts of crayfish Procambarus clarkii against CCl4 (4 mM) induced toxicity in the human hepatoma cell line (HepG2). Pretreatment of HepG2 cells with increased concentrations (100, 150, and 200 µg/mL) of alcoholic or n-hexane extract of crayfish Procambarus clarkii 1 h before exposure to CCl4 for 24 h significantly reduced the cytotoxicity induced by CCl4, enzymatic activities of alanine transaminase (ALT) and aspartate transaminase (AST), and malondialdehyde (MDA) levels. Besides, the HepG2 cells pretreated either with 200 µg/ml of alcoholic or n-hexane crayfish extract 1 h before exposure to CCl4 for 24 h showed a normal cellular morphology contradictory with apoptotic features in the cells exposed only to CCl4. Our results revealed that alcoholic and n-hexane extracts of crayfish Procambarus clarkii exert hepatoprotective actions on HepG2 cells towards the CCl4-induced cytotoxicity through their antioxidant action.