The chicken anemia virus protein, apoptin, which manifests selectivity and specificity to tumor cells, induces a p53-independent and Bcl-2-insensitive type of apoptosis in various human tumor cells. In this study, the apoptin gene was cloned from the total DNA of chicken anemia virus, and the recombinant vector was constructed. We used oligonucleotide microarray to study the changes of four genes, including Bcl-2, Bcl-x_L, Bad and Bax. The post-transfection with the recombinant was also studied. The pro-apoptotic genes(Bad and Bax) and anti-apoptosis genes(Bcl-2 and Bcl-x_L) were up-regulated in contrast to the controls. According to the published data, either Bcl-2 or Bcl-x_L can form non-functional heterodimers by Bad and Bax binding together, resulting in blocking partly the release of cytochrome c from mitochondria. However, apoptosis could be inhibited by neither the endogenous Bcl-x_L nor Bcl-2 over-expression. The experiments show that the apoptin-induced apoptotic pathway is related to the up-regulation of Bad and Bax. Bad was up-regulated by apoptin; then this up-regulated product of Bad was in favor of displacing Bax from binding to Bcl-x_L or Bcl-2. Consequently, Bax exerted a pro-apoptotic dysfunction to mitochondria, thereby inducing the release of cytochrome c. Finally, apoptin induced the apoptosis of HHCC cells. These results indicate that the oligonucleotide microarray can reveal the genes related to the apoptosis induced by apoptin in HHCC cells. The chicken anemia virus protein, apoptin, which manifests selectivity and specificity to tumor cells, induces a p53-independent and Bcl-2-insensitive type of apoptosis in various human tumor cells. In this study, the apoptin gene was cloned from the total DNA of chicken anemia virus, and the recombinant vector was constructed. We used oligonucleotide microarray to study the changes of four genes, including Bcl-2, Bcl-x_L, Bad and Bax. The post-transfection with the recombinant was also studied. The pro According to the published data, either Bcl-2 or Bcl-x_L can form non- functional heterodimers by Bad and Bax binding together, resulting in blocking part the release of cytochrome c from mitochondria. However, apoptosis could be inhibited by neither the endogenous Bcl-x_L nor Bcl-2 over-expression. The experiments show that the apoptin-induced apoptotic pathway is re lated to the up-regulation of Bad and Bax. Bad was up-regulated by apoptin; then this up-regulated product of Bad was in favor of displacing Bax from binding to Bcl-x_L or Bcl-2. -apoptotic dysfunction to mitochondria, thereby inducing the release of cytochrome c. Finally, apoptin induced the apoptosis of HHCC cells. These results that the oligonucleotide microarray can reveal the genes related to the apoptosis induced by apoptin in HHCC cells.