Sida rhombifolia ssp. retusa is a well established drug in the Ayurvedic system of medicine used forantirheumatism and antiasthmatism. Inhibitory effects of S. rhombifolia ssp. retusa seed extract on DEN inducedhepatocellular preneoplastic foci and carbon tetrachloride (CCl4) induced hepatotoxicity was investigated inrats. Rats received DEN, 1ppm/g b.w. in drinking water for 6 weeks or CCl4, 0.7 ml/kg i.p. once a week for 4weeks and seed extract 50 mg, 100 mg/kg b.w. orally prior, during and after exposure to DEN/CCl4 for 20 or 5weeks, respectively. Treatment with seed extract significantly inhibited the increase in DEN/CCl4 induced activitiesof pre-cancerous marker enzymes; gamma-glutamyl transpeptidase, glutathione-S-transferase, hepatotoxicitymarker enzymes; glutamate pyruvate transaminase, glutamate oxaloacetate transaminase and alkalinephosphatase as well as lipid peroxidase. Depleted glutathione, protein and albumin levels were restored. Also,histopathological and transmission electron microscopic studies showed prevention of cellular degenerativechanges. The chemopreventive and hepatoprotective potentials of seed extract are due to free radical scavengingactivity and restoration of cellular structural integrity.