The economic damage caused by H5N1 avian influenza virus outbreak in domestic poultry and the threat of this virus to human health make the research of this virus highly significant. During the 2004 outbreak of avian influenza in Hubei province, People´s Republic of China, we isolated a new H5N1 subtype avian influenza virus named as A/chicken/Hubei/489/2004(H5N1) (shorten as AIVHubei489 here). In this study, the infectivity and apoptosis-inducing characteristics of AIVHubei489 were studied. We demonstrated that AIVHubei489 could infect MDCK cells and the infection induced apoptosis. Our data also showed that the apoptosis induced by this virus in MDCK cells was caspase activity dependent. Moreover, we proved that caspase 8 but not caspase 9 was involved in this apoptosis. The infectivity and apoptosis-inducing activity of AIVHubei489 in Vero and HeLa cells were also studied. Our results showed that AIVHubei489 could replicate in Vero and HeLa cells, but the infection did not cause apoptosis in either of the two cell lines. Thus, AIVHubei489 induced apoptosis through a caspase-dependent pathway in a cell-specific manner.