Many malignant tumors become resistant to tumor necrosis factor-alpha (TNF-α)-inducedcelldeathduring carcinogenesis. In the present study, we examined whetherparkinacts as a tumor suppressor in HeLacells, a humancervicalcancercellline resistant to TNF-α-inducedcelldeath. TNF-α-treatment alone did not affect HeLacellviability. However, expression ofparkinrestored TNF-α-induced apoptosis in HeLacells. Increasedcelldeathwas due to the activation of theapoptoticpathway. Expression ofparkinin TNF-α-treated HeLacellsstimulated cleavage of the pro-apoptoticproteins caspase-8, -9, -3, -7 and poly ADP ribose polymerase (PARP). In addition,parkinexpression resulted in decreased expression of the caspase inhibitory protein, survivin. These results suggest thatparkinacts as a tumor suppressor in humancervicalcancercellsby modulating survivin expression and caspase activity. We propose that this pathway is a novel molecular mechanism by whichparkinfunctions as a tumor suppressor.