Tobacco smoking and hepatic damage causes oxidative stress in humans and underlay numerous chronic degenerative diseases. Heavy smoking yields toxins which induce necroinflammation and increase the severity of hepatic lesions. Accordingly, the main object of this study to investigate the effect of chrysin against thioacetamide (TAA)-induced liver injury in rats exposed to tobacco smoke in combination. The study was carried out by investigating the oxidative stress biomarkers (glutathione peroxidase, SOD, catalase, paroxynase-1 and NAD (P) H: quinoneoxidoreductase 1 activities), inflammatory markers (IL-6 and IL-8 levels and gene expressions of NF-κB and VEGF) as well as histopathogical examination. It was found a significant reduction in activities of antioxidant enzymes concomitant with cytokines elevation; (IL-6 and IL-8) in rats exposed to tobacco smoke in combination with (TAA) treatment compared with normal control. Additionally, the transcript levels of (NF-κB and VEGF) genes were significantly higher in the rats exposed to tobacco smoke in combination with (TAA) treatment compared with normal control. However, treatment with chrysin, the levels of these parameters were significantly decreased which demonstrates the ameliorative effect of chrysin against (TAA) induced liver injury in rats exposed to tobacco smoke in combination. Histological investigations revealed that chrysin gave more preventive effect against thioacetamide (TAA)-induced liver injury in rats exposed to tobacco smoke. In conclusion, chrysin modulated the damage induced by exposure to tobacco smoking and hepatic disease