The underlying molecular mechanisms of the antihepatotoxic activity of Trianthema portulacastrum by monitoring its effect on mouse liver DNA-chain break, sugar-base damage and chromosomal aberrations, during chronic or acute treatment with carbon tetrachloride (CCl4) have been studied. Daily oral feeding with the ethanolic extract (150mg/kg basal diet, per os) was given 2 weeks before CCl4treatment and continued until the end of the experiment (13 weeks). T. portulacastrum extract offer unique protection (P< 0.05–0.001) against the induction of liver-specific structural-type chromosomal anomalies 15, 30 or 45 days after the last CCl4insult, compared to control mice. This was further evidenced by extract-mediated protection (15 days prior feeding following a single necrogenic dose of CCl4) of the generation of DNA chain-break and Fe-sugar-base damage assays. The observed hepatoprotective mechanism could be due to its ability to counteract oxidative injury to DNA in the liver of mouse.