Through analysis of genome-wide expression profiles, we have been attempting to isolate novel molecular targets for diagnosis, treatment and prevention of hepatocellular carcinoma (HCC). Among the genes that a cDNA microarray showed to be commonly transactivated in HCCs, we identified a novel human homologue of the Drosophila Van Gogh/Strabismus gene and termed it VANGL1 [Vang (Van Gogh, Drosophila)-like 1]. This gene, which encoded a transcript with an open reading frame of 1,572 bp, was expressed specifically in testis and ovary among 16 adult normal tissues examined. Transfection of antisense S-oligonucleotides, but not of sense S-oligonucleotides, into hepatoma cells suppressed expression of VANGL1 and subsequent growth of these cells was inhibited to a marked degree. The findings suggest that VANGL1 might serve as a diagnostic marker for HCC as well as a potential molecular target for development of novel therapeutic drugs.