The extraordinary versatility of gene therapy opens new possibilities for the treatment of incurable diseases, including hepatocellular carcinoma. Gene therapy strategies against tumors include prodrug activation therapy by the transfer of suicide genes, immunogene therapy, tumoral cell phenotype correction by the inhibition of oncogenes or the transfer of tumor suppressor genes, antiangiogenesis and transfer of oncolytic viruses. The experience accumulated during the last decade of clinical gene therapy indicates that genes can be expressed inside the tumor tissue, but the overall results of the studies conducted so far are still disappointing, mainly due to the poor performance of the currently available gene therapy vectors. This review covers the general aspects of gene therapy vectors, preclinical data available in animal models of hepatocellular carcinoma, and finally a brief summary of the gene therapy clinical trials aimed at the treatment of liver cancer.

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