The overexpression of crystallin-αB confers protection against ischemia/reperfusion, hypoxia/reoxygenation, hypertonic stress and reactive oxygen stresses. Some evidences have suggested that increasing the expression of crystallin-αB represents a potential therapeutic strategy for the cardiac injury. In this study, we studied the potential cytoprotective effect of HSP27 as a therapeutic protein using protein transduction domain system in cardiac cells. Crystallin-αB gene was fused with a gene fragment encoding TAT protein transduction domain in a bacterial expression vector. TAT-crystallin-αB protein was rapidly transduced into cardiac cells. Its transduction showed cytoprotective effect against the hypoxic stress, which was accompanied by reduced caspase-3 activity. These results suggest that delivered TAT-crystallin might protect cell death from hypoxic stress by modulating caspase activation pathway in vitro and this may be of potential therapeutic benefit in ischemic diseases.