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Liver is one of the vital organs of the animal body and plays a central role in transforming and clearing the chemicals, but is susceptible to the toxicity from these agents.Some chemical agents, such as those used in laboratories and industries, natural chemicals and herbal remedies can also induce hepatotoxins.The present study was undertaken to prepare yeast enriched with selenium in proper concentration to achieve a balance between Se incorporation and optimum growth and viability of yeast cells.Additionally, the study aimed at assessing the safety of chronic administration of Se as Se-yeast in comparison with Se as sodium selenite form in experimental animals.Furthermore, the study was extended to evaluate the protective role of the Se-yeast against thioacetamide-induced hepatotoxicity in rats. It was found that the treatment with Se, yeast or Se-yeast produced significant protection against thioacetamide-induced hepatotoxiocity as indicated by marked improvement in the studied biochemical markers and histopathological feature of liver tissue with special reference to Se-enriched yeast which showed the most pronounced effect.