A goal of cancer research is to develop therapies that can selectively kill tumor cells without adversely affecting normal cells. In the case of hepatocellular carcinoma (HCC), there is a possibility that this goal may be achieved by introducing a cytotoxic gene under the control of transcriptional regulatory sequences of the a-fetoprotein (AFP) gene. The expression of the therapeutic gene should be limited to AFP-positive cells (i.e., HCC), so that only tumor cells will be eliminated without harming normal cells. In this article, we will first review the main features of human AFP regulatory sequences with respect to tumor-specific transcriptional activity. We then describe details of an adenoviral vector carrying the human AFP regulatory sequences used for HCCdirected gene therapy.