The avian reovirus (ARV) infection is associated with various disease conditions in poultry. However, the pathogenesis mechanisms are poorly characterized. In the present study, we clearly demonstrated that the σC of ARV S1133 strain induced apoptosis in both BHK-21 and Vero cells. Five kinds of assays for apoptosis were used in analyzing ARV-infected BHK-21 and Vero cells: (1) assay for DNA ladders, (2) ELISA detection of cytoplasmic histone-associated DNA fragments, (3) nuclear staining with acridine orange, (4) Western blot, Northern blot, and immunofluorescent assay (IFA), and (5) flow cytometric analysis. The σC protein of ARV could elicit apoptosis occurring in a dose- and time-dependent manner. The current results further our understanding of the function of σC in cultured cells and suggest that σC is a viral-encoded apoptin and possesses apoptosis-inducing ability. Furthermore, deletion analysis of the ARV σC protein suggests that the carboxyl-terminus of σC is important in mediating σC-induced apoptosis because its deletion abolished the induction of apoptosis.