Aflatoxin B₁ (AFB₁) is a potent mycotoxin in humans and animals. The exposure to AFB₁ is evidenced to implicate multi-organ toxicity in humans and animals, particularly hepatotoxicity. Genkwanin (GNK) is a bioactive non-glycosylated flavonoid with potential pharmacological properties. Therefore, the current study aimed to determine the dose-dependent role of GNK against AFB₁-instigated hepatotoxicity. The investigation was carried out on 96 adult male albino rats, which were equally distributed into eight groups. The effect of 3 different doses of GNK (5, 10 and 20 mgkg-1) was evaluated against the toxicity elicited by 50 ugkg^-1 of AFB_1. After the administration of AFB1 and GNK by the oral gavage for 56 days, the biochemical and hepatic serum markers were determined in addition to histopathological observation. AFB₁ exposure disrupted the biochemical profile by declining the activities of antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and glutathione content), while elevating the concentration of reactive oxygen species and malondialdehyde level. Furthermore, AFB₁ exposure notably elevated the levels of hepatic serum enzymes (alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase) along with the levels of inflammatory markers, nuclear factor kappa-B, tumor necrosis factor-α, Interleukin-6, Interleukin-1β and activity of cyclooxygenase-2. Besides, AFB₁ induction caused histopathological impairments in hepatic tissues. Nonetheless, GNK co-administration remarkably ameliorated all the damages of the hepatic system induced by AFB1 administration to the rats. Therefore, it was demonstrated that the GNK could potentially cure AFB₁-instigated hepatotoxicity attributing to its antioxidative and ant-inflammatory potential.