Thioacetamide (TAA) is an organosulfur compound used as a sulfur donor in many industrial pharmaceuticals. The exposure to TAA could happen through inhalation, ingestion, and injection. It resists biodegradation and causes liver necrosis and fibrosis. In the current study, twenty male Sprague Dawley rats (160-200g) were divided into two groups (control group and TAA group, n=10). In the TAA group, the rats received an intraperitoneal (i.p) dose of TAA at 150 mg/kg/biweekly/nine weeks. The mortality rates were calculated at the end of the experiment. The values of alkaline phosphatase (ALP) and total bilirubin (T.B) were estimated in serum. The livers were examined macroscopically, microscopically, and ultrastructurally to detect any pathological alterations. According to the results, the TAA group recorded high mortality rate (50%) indicating liver failure. Additionally, the same group showed significant increases in the serum ALP and T.B. TAA induced severe liver cirrhosis represented by irregular nodular liver surfaces, besides, the presence of prominent neoplastic masses in the gross examination. The microscopic examinations revealed diffuse replacement of the hepatic parenchyma by thick fibrous tissue surrounding the regenerative hepatic nodules, dysplastic megahepatocytes with nuclear changes, and development of tubular hepatocellular carcinoma. Moreover, the ultrastructural examination showed nuclear changes, massive mitochondrial damage and fragmentation of the rough endoplasmic reticulum. In conclusion, chronic exposure to TAA induced serious alterations in the livers of rats biochemically, macroscopically, microscopically, and ultrastructurally. Therefore, it is a life-threatening and a public health hazard toxin. High safety precautions should be applied before/during the exposure to TAA.