Hepatocellular carcinoma is the fourth common cancer globally occurring by many factors such as mycotoxins, chemicals, genetical, viral factors etc. AFB1 is a potent mycotoxin classified in group I carcinogens by IARC found in contaminated food stuffs. The present study was aimed at evaluating the ethanolic extract of whole plant of sida cordifolia L against AFB1 induced HCC. Hepatocellular carcinoma (hepatoma) was induced in wistar rats by intra peritoneal administration of AFB1 (250μg/kg/dose) for 7 days. The effect of concurrent administration of ethanolic extract of sida cordifolia L. at doses of 250mg/kg and 500mg/kg were given orally was observed by estimating the serum levels of SGOT, SGPT, ALP, LDH, GGT and TP. DNA, RNA and TP were estimated from liver. Antioxidant and pro-oxidant studies were also measured. The results showed a significant decrease in serum SGOT, SGPT, ALP, LDH and GGT and increase in total proteins of groups treated with EESC. Elevated DNA and RNA found decreased with a prominent increase in total proteins in liver of EESC groups. Significant increase in antioxidants and a decrease in lipid peroxidation were also observed. The extracts at both doses (250mg/kg and 500 mg/kg b.w) shows a significant (p<0.001) reversal of altered biochemical, molecular and antioxidant parameters showing that sida cordifolia L. possess antioxidant and antitumor activity.