Alpha-Manganese dioxide (alpha-MnO2) nanowires are used as electrode materials to significantly enhance the performance of lithium batteries. In this study, we investigate the nanotoxicity of alpha-MnO2 nanowires toward Hela cells. The alpha-MnO2 nanowires, which were successfully synthesized using the hydrothermal approach, can induce cytotoxicity dose-dependently in Hela cells. The accumulation of reactive oxygen species (ROS) and depletion of glutathione (GSH) are also observed in the nanowire-treated cells. In addition, comet assays and cell nucleus morphology show that both DNA damage and cell apoptosis occur in the nanowires exposure group. Based on these results, a mechanism for alpha-MnO2 nanowire-induced cytotoxicity in Hela cells, which involves the accumulation of ROS, formation of oxidative stress, DNA oxidative damage and cell apoptosis, is proposed. This investigation may provide a fundamental insight to understand the nanotoxicity of wire-shaped nanomaterials.