Expression of HERPUD1 was obviously increased around the hematoma in rat ICH model. The expression of apoptosis markers including cytochrome c (cyt c) and active caspase-3 increased accompanied to HERPUD1 in vivo. HERPUD1 silence brought about up-regulation of cyt c and active caspase-3 coupled with increased cell apoptosis in vitro model. HERPUD1 might play a protective role in ICH-induced neuronal apoptosis in rat models. ER stress might play a part in the complicated and various mechanism of ICH.