Hepatocellular carcinoma (HCC) is a complex liver disease with limited treatment options
and often resulting in a poor prognosis. The development of HCC depends on the formation of new
blood vessels and it demonstrates hypervascularity and invasive property to the surrounding vasculature
clinically. A complex network of growth factors acting on both tumor cells and endothelial cells
mediates the angiogenesis in HCC. It is an attractive approach to inhibit the angiogenic processes as
the treatment of HCC and therefore, anti-angiogenic TKIs were developed to inhibit the vessel formation in the tumors.
However, it is currently perceived that the efficacy of these anti-angiogenic TKIs has reached plateau, and it is necessary
to develop novel agents with non-TKI mechanism to inhibit the angiogenic targets. With the better understanding of molecular
mechanisms that govern angiogenesis, as well as the advancement in biomedical engineering, new approaches of
gene therapy have brought hopes for therapeutic intervention in HCC. Gene therapy is based on the transfer of genetic material
to the patients with the aim to modify or correct the malignancy from its molecular basis. In this article, we will discuss
the conventional anti-angiogenic therapies and the gene therapy approaches in HCC. The therapeutic potential of
gene therapy for HCC treatment has been demonstrated and further development of anti-angiogenic may result in new
treatment option for HCC patients.