A composite EBV-based expression vector, pEBAF, was constructed with the 5'-flanking sequence of human alpha-fetoprotein gene as a promoter. Complexed to galactosylated histone, this vector with a foreign DNA insertion could be transferred into hepatic cells via the asialoglycoprotein receptor mediated endocytosis pathway. It was replicated as an episome, and its expression was restricted to the AFP positive hepatoma cells. This new gene delivery method has the following advantages: (i) absence of a potential toxicity is related to viral vectors; (ii) the targeting is specific to AFP positive hepatoma cells; (iii) the introduction of the EBV replicon into this system results in the high level expression and long-term maintenance of the transferred gene. This novel gene delivery system has potential applications in gene therapy for the treatment of hepatocellular carcinoma.