Objective: To investigate the hepatoprotective efficacy of 6-gingerol against acetaminophen-induced hepatotoxicity in mice. Methods: Mice were injected with a single dose of acetaminophen (900 mg/kg) to induce hepatotoxicity, while 6-gingerol (30 mg/kg) or the standard drug silymarin (25 mg/kg) was given 30 min after the acetaminophen administration. The mice were sacrificed 4 h after acetaminophen injection to determine the activities of liver marker enzymes such as aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), total bilirubin in serum, and lipid peroxidation and antioxidant status (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione transferase and glutathione) in liver homogenate. Results: The treatment of 6-gingerol and silymarin to acetaminophen-induced hepatotoxicity showed significant hepatoprotective effect by lowering the hepatic marker enzymes (AST, ALT, and ALP) and total bilirubin in serum (P<0.05). In addition, 6-gingerol and silymarin treatment prevented the elevation of hepatic malondialdehyde formation and the depletion of antioxidant status in the liver of acetaminophen-intoxicated mice (P<0.05). Conclusion: The results evidently demonstrate that 6-gingerol has promising hepatoprotective effect which is comparable to the standard drug silymarin.