Background: Cancer defines malignant neoplasms characterized by metastatic growth. Links between inflammation, proliferation and apoptosis leading to pathogenesis of cancer complications have long been suspected, but its molecular nature remains still unclear. The chemotherapeutic agents currently in use are still unsatisfactory. So prevention and early diagnosis are the only effective tools against this tumor whose incidence and mortality rates are highly increased during the last decade in liver cancer populations. Therefore the search for novel therapeutic approaches is warranted. Objective: The study was conducted to identify the antiproliferative and cytotoxic activity of the new compound on liver cancer. Methodology: Group I - Control animals, Group II- cancer induced animals, Group III __ampersandsignndash; pretreated animals, Group IV - cancer bearing animals post treated with Withaferin-A (WFA), Group V- drug control. Result: Withaferin-A was tested for its capability to inhibit cell growth on hepatocellular carcinoma established from rat tissue samples. The immunohistochemical expressions of HGF, PCNA proteins and their potential role as prognostic factors in rats with hepatocellular carcinoma were studies. WFA potently inhibited proliferation of the liver cancer cells by down regulate expression of HGF, PCNA oncoproteins. Conclusion: Findings in this study demonstrated that the Withaferin-A has the antiproliferative activity in hepatocellular carcinom