Olfactory ensheathing cell (OEC) transplantation is one promising technology for the treatment of spinal cord injury. Many studies have been focusing on the functional improvement after OEC implantation in spinal cord injury of animals. However, little is known about the mechanisms about how OECs respond to the proapoptotic microenvironment after transplantation. We use the hypoxia and serum deprivation (HSD) paradigm in OECs to evaluate the effects of the ischemic damage. OECs underwent caspase-dependent apoptosis during HSD and a pan-caspase inhibitor specifically blocked the cell death. In addition, HSD resulted in a time-dependent decrease of mitochondrial membrane potential DeltaPsi(m), triggering a transient increase in p53 content and activated p53 in a time-dependent manner. In summary, our data suggest that HSD trigger apoptotic OECs death, which may be related to mitochondria dysfunction and the dependence of p53.