Our recent findings indicate an induced upregulation of 14-3-3gamma mRNA and protein in ischemic cortical astrocytes. Despite being brain-specific, the functional role of 14-3-3gamma in the brain still remains largely unknown. In this study, we show that among all the 14-3-3 isoforms, only the gamma isoform is inducible under ischemia in astrocytes. Furthermore, this upregulation of 14-3-3gamma may play a specific protective role in astrocytes under ischemia. Overexpression experiments and antisense treatment show that an elevation of 14-3-3gamma protein in astrocytes promotes survival, while a decrease in 14-3-3gamma enhances apoptosis in astrocytes under ischemia. Under ischemia, endogenous 14-3-3gamma binds p-Bad, thus preventing Bad from entering mitochondria to initiate apoptosis. Therefore, 14-3-3gamma is selectively induced during ischemia to protect astrocytes from apoptosis through p-Bad-related signaling.