Cytokine-induced apoptosis inhibitor 1 (CIAPIN1) protein is widely expressed in the brain and it is known that this protein is involved in cell survival including dopaminergic neuronal cells. Oxidative stress is known as one of the major causes of degenerative diseases including ischemia. In this study, we investigated the effect of CIAPIN1 protein on hippocampal neuronal (HT-22) cell damage induced by hydrogen peroxide (H₂O₂) and in an animal model of ischemia using Tat-CIAPIN1 fusion protein which can transduce into cells. Tat-CIAPIN1 protein transduced into HT-22 cells and significantly inhibited cell death, DNA fragmentation, and reactive oxygen species (ROS) generation. Also, Tat-CIAPIN1 protein enhances cell survival via the regulation of Akt, MAPK, NF-κB and apoptotic signaling pathways in the H₂O₂ treated cells. In an ischemic animal model, Tat-CIAPIN1 protein transduced into the brain and protected neuronal cell death of hippocampal CA1 region induced by ischemic insult. In conclusion, we demonstrated that Tat-CIAPIN1 protein has protective effects against hippocampal neuronal cell damage induced by ischemic injury, suggesting that Tat-CIAPIN1 protein may provide a potential therapeutic agent for ischemia.