The aim of this study was to investigate the effect of tetrodotoxin (TTX) extracted from puffer fish Lagocephalus sceleratus on hepatotoxicity induced by carbon tetrachloride (CCl₄). Adult male albino mice were divided into four groups: 1) control group treated with saline; 2) CCl₄ group; 3) mice injected with 5 doses of TTX (1 µg/kg) and 4) mice injected with 5 doses of TTX (1 µg/kg) then treated with CCl₄ for 6 weeks. The results showed that injection with 5 doses of TTX extract significantly reduced the impact of CCl₄ toxicity on the serum markers of the liver, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and albumin (Alb). However, the biochemical results of TTX group were significantly different from the control group. On the other hand, the histologic examination of liver sections from mice given CCl₄ showed hyperplasia of bile ducts, excessive fibrosis in portal areas associated with detachment from parenchyma and lymphocytic infiltration. Other damaging features were microvesicular fatty change, pyknotic nuclei, karyolytic nuclei, irregular dilated sinusoids with active Kupffer cells and some hepatocytes showed necrosis. On the other hand, mice injected only with TTX showed an almost normal pattern with few random sites of hydropic degeneration. While the liver sections from TTX + CCl₄ group showed noticeable hydropic degeneration, lymphocyte infiltration, and hemorrhage especially in the portal area. However, no signs of fatty degeneration or excessive fibrosis were observed like those noticed in case of CCl4. Moreover, no signs of coagulate necrosis or lytic necrosis were noticed. It can be concluded that treating with TTX extracted from puffer fish, Lagocephalus sceleratus decreased the damaging effect of CCl₄ on the liver of albino mice.