Hydroquinone (HQ) is extensively utilized in various industrial applications and as a dermatological agent
however, its metabolic processes and toxicological effects, particularly in the liver, remain insufficiently understood. This study aimed to investigate the impact of different doses of HQ on liver injury and lipid metabolism in C57BL/6 mice, with a specific focus on the SCD1/AMPK signaling pathway. We administered HQ at doses of 0, 12.5, 25.0, and 50.0 mg/kg over a period of 13 weeks, followed by biochemical analyses, RNA sequencing, and Western blotting to elucidate the underlying mechanisms. Our findings indicated that lower doses of HQ (12.5 and 25.0 mg/kg) led to lipid accumulation in the liver, accompanied by increased liver TG and serum TC. In contrast, the highest dose (50.0 mg/kg) resulted in elevated liver enzyme levels, indicative of liver damage, while lipid levels decreased. Notably, the mRNA or protein levels of SCD1 were upregulated in response to the lower doses of HQ (12.5 and 25.0 mg/kg), whereas AMPK activation and enhanced autophagy were observed in the 50.0 mg/kg HQ-treated group, reflecting an energy stress response. These findings suggest that lipid dysregulation may serve as an early indicator of HQ-induced liver injury, and that the SCD1/AMPK pathway may play a protective role against chemically induced hepatotoxicity. This study offers new insights into the toxicological effects of HQ on the liver and underscores the necessity for further exploration of the protective mechanisms of SCD1 and AMPK in mitigating HQ-induced hepatotoxicity.