© 2022 Verduci Editore s.r.l. All rights reserved.OBJECTIVE: Acetaminophen (APAP) is one of the most commonly used analgesics and antipyretics. It causes serious liver damage when taken in large quantities by adults or children. Also, 6-shogaol is an active compound obtained from ginger with anti-inflammatory and antioxidant properties. This study aimed at examining the therapeutic effect of 6-shogaol in APAP-induced hepatotoxicity. MATERIALS AND METHODS: The mice were separated into five groups. After the mice were sacrificed, the levels of alanine aminotransferase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) in the blood, glutathione (GSH) level in the liver tissue homogenate, and levels of induced nitrite oxide synthetase (INOS) and total nitrite/nitrate were measured by spectrophotometric methods. RESULTS: APAP administration significantly increased the serum levels of ALT, AST, and ALP, INOS activity in liver tissue, and total nitrite/nitrate levels compared with control and significantly decreased GSH levels. After APAP toxicity, 6-shogaol and N-acetylcysteine (NAC) administration significantly decreased the levels of ALT, AST, INOS, and total nitrite/nitrate levels and significantly increased GSH levels compared with control. Also, 6-shogaol was found to be better than NAC in increasing the GSH level. CONCLUSIONS: The study showed that 6-shogaol might have an early therapeutic effect on APAP-induced liver damage.