The aim of the present work was to evaluate the effect of copper (I)-nicotinate complex (CNC) on experimentally 4-Dimethylaminoazobenzene (DAB)-induced hepatocellular carcinoma (HCC) in male rats. In addition to the histopathological examination we measured hepatic glutathione content, malondialdehyde, nitric oxide levels, lamin B1 m-RNA, caspase-3 activity and serum interleukin-12 level after 2, 4, 6, 8 months from commencement of the experiment. Results: histopathological examination showed HCC development after 4 months of DAB administration. The hepatic glutathione content, lamin B1 m-RNA and nitric oxide levels were significantly elevated, while malondialdehyde, interlukin-12 levels and caspase-3 activity were significantly decreased with the progression and development of the HCC. On the other hand, administration of CNC one month before DAB delayed the development of neoplastic growth to the 8th month. Interestingly, when CNC was administered one month after DAB, it successfully prevented HCC development throughout the whole experiment as confirmed by histopathological data and explained by biochemical markers, as glutathione, lamin B-1 and nitric oxide were significantly declined but malondialdehyde, interlukin-12 and caspase-3 activity were significantly elevated compared to that in corresponding control group. Conclusion: CNC was able to delay or prevent HCC development in rats fed with the potent liver carcinogen DAB. Our data shows that CNC exerts its anti-tumour effects through modulating oxidative stress status as well as the machinery of apoptosis and angiogenesis. Therefore, CNC may be used as a potential protective anticancer agent.