Hepatocellular carcinoma with high incidence and poor survival stands as a major global health burden. Various challenges involved in drug therapies impede their efficacy for substantial protective effects. They emphasize the necessity for the development of safe and affordable options suitable for long-term treatment. The present study has explored the therapeutic potential of traditional Dawa-ul-kurkum formulation for anticancer effects against hepatocellular carcinoma (HCC). The formulation and its individual ingredients were screened for cytotoxic effects, induction of apoptosis, and cell cycle arrest on HepG2 cell line. Dawa-ul-kurkum was further evaluated for regression of tumor growth in diethylnitrosamine (DEN) induced HCC rat models. Low, medium, and high doses of the formulation were fed orally to the test groups. A Combination of Dawa-ul-kurkum with the anticancer drug Doxorubicin was tested for assessment of adjuvant therapy. The classical dosage form with honey of each ingredient plant drug displayed enhanced cytotoxic effect and pharmacologically significant IC50 values. The Dawa-ul- kurkum formulation was superior in inducing apoptosis and arresting cells in the G0-G1 phase of the cell cycle. Significant regression of tumor growth and reversal of biochemical parameters in DEN-induced HCC rat study endorsed its prominent anticancer effect. The promising potential to induce apoptosis, cell cycle arrest, and regression in tumor growth validated the traditional Dawa-ul-kurkum formulation for anti-hepatoma activity. The study convincingly promotes the use of Dawa-ul-kurkum formulation for the development of a cost-effective and safe therapeutic strategy against HCC.