TDP-43 is a ubiquitously expressed DNA/RNA binding protein that has recently attracted attention for itsinvolvement in neurodegenerative diseases. While TDP-43 has been found to participate in various importantcellular activities including stress and apoptosis, little is known about its role in cancer cells. Here we report thatstaurosporine (STS) induced apoptosis in U87 glioma cells is associated with rapid downregulation of TDP-43at both mRNA and protein levels. The latter is dependent on activation of caspase 3. More importantly, we haveshown that knockdown of TDP-43 by specific siRNA dramatically enhanced cytotoxicity of STS. These resultssuggest that normal level of TDP-43 may be protective for cancer cells under apoptotic insult.