In the present investigation, the efficacy of berberine in human lung carcinoma cell line (A549) and experimental lung cancer were studied. The viability of A549 cells was significantly reduced by berberine treatment, indicating that the treatment is cytotoxic. This was confirmed from the results that levels of marker enzymes and synthesis of nucleic acids were reduced on berberine treatment.Similarly the increased level of intra cellular calcium, p53 protein expression and cytochrome C paves the way for caspases activation; thereby induction of apoptosis and cell cycle arrest ensues that indicates the anti- proliferative potential and anticancer activity of berberine. Moreover, on berberine treatment, the lung cancer bearing animals have showed significant increase in body and organ weight. The lipid peroxidation and glycoproteins levels were decreased on treatment. Altered activities of membrane bound ATPase, Phase I biotransformation enzymes and the levels of ICDH, SDH, MDH and ? – KGDH due to mitochondrial damage were noticeably reverted back to near normal in treated animals. Histopathological studies confirm the recovery from the neoplastic conditions.