Hepatitis B and C viruses are the etiologic agents of most cases of the world's most common cancer: hepatocellular carcinoma (HCC). The incidence of this cancer is rising globally, due largely to the epidemic spread of HCV infection. It is thus essential that means be found to prevent this lethal disease by prophylactic and therapeutic immunization. DNA-based immunization has the ability to induce both cell-mediated and humoral immunity, and thus lends itself to therapeutic immunization strategies. DNA-based immunization also lends itself to the design of multivalent immunogens targeted at various pathogens. This strategy will facilitate economical immunization in the developing world. DNA-based immunization has protected chimpanzees against HBV challenge and, in combination with recombinant canarypox boosters, has downregulated chronic HBV infection in a chimpanzee. DNA-based immunization is still in its infancy for HCV infections. Substantial immunogenicity has been demonstrated, particularly in mice; however, enhancement of immunogenicity will be required to achieve prophylactic or therapeutic efficacy.