Titanium dioxide nanoparticles have multiple beneficial uses, as they are used in many medical, industrial, economic, and other fields. Despite these many benefits, it is not without harm to humans and animals if used without control. Therefore, the present study aimed to discover the histopathological effects of Titanium dioxide nanoparticles on the liver of Japanese quail, Coturnix coturnix japonica. The study included three groups, the first group, the control group, which were dosed with distilled water for four continuous days, and the second and third experimental groups, which were dosed with Titanium dioxide nanoparticles at a concentration of 20 and 40 mg/kg, respectively. Four, fourteen, thirty and sixty days after the experiment began, the birds were sacrificed. The results showed the emergence of many histological lesions in the liver of birds of the two experimental groups, to varying degrees, in the four periods, among the most prominent tissue lesions that appeared in the second experimental group, the emergence of necrosis, hemorrhage, vacuolation, congestion, ballooning swelling, in addition to infiltration of inflammatory cells. While in the third experimental group, histopathological lesions appeared similar to second group, in addition to sinuses dilatation, Kupffer cells hypertrophy, hepatocyte enlargement, and necrosis of the walls of blood vessels and bile ducts. The study concluded that direct exposure to Titanium dioxide nanoparticles leads to damage to the liver tissue of these birds, which may affect its function and thus endanger its life.