Objective To study the death mode and mechanism of HeLa cancer cell induced by five strain bluetongue virus(BTV). Methods Transmission electron microscope(TEM) was introduced to study changes of ultrastructure. Growth and apoptosis of HeLa cell infected with bluetongue virus were detected with MTT assay and flow cytometry. DNA fragmentation and the activity of caspase-3, -8, -9 were determined by colorimetric assay. Results Many HeLa cells which infected with BTV were observed apoptosis and lyse, and in the plasma were found many viral inclubodies and subviral particles without outer layer proteins. BTV could inhibit HeLa cell proliferation moderately and different serotypes of virus had different effect. Various stages of apoptotic cells were found by flow cytometry and the percentage of apoptosis caused by five strain bluetongue virus were not the same. DNA-Ladder was typical. Caspase-3,-8 ,-9 activity were increased by varying degrees. Conclusion BTV could infect in HeLa cell efficiently and induce it to apoptosis in vitro, then different serotypes of virus have different effect.