Background: As brain tumor cells are immunologically active, they release various factors like a cytokine, growth factor and express a death domain on their surfaces. Accordingly they support proliferation, vascularity, invasiveness and maintain immune privileged sites. However, the relationship between tumor cells and surrounding neuron cells have been rarely reported in tumor patients with epilepsy that inhibitory neuron cells have been lost around peritumoral sites. This study was designed to address that tumor cells directly damage neuron cells. Methods: Using LDH assay and special stain, we investigated whether or not cultured supernatants of astrocytoma cells induce the damage of neuron cells. Results: The neuron cells were killed by tumor cells supernatant and increased by pretreatment of neuron cells super-natant and lysates. Protein extracted tumor cells supernatant also damage neuron cells. It was proved by Annexin-PI stain and DNA fragmentation that neuronal death by tumor cells was apoptosis. The more malignant tumor cells, the more neuronal death was induced and the more their cytokines were expressed. In comparison with various cytokine expres-sions in tumor cells, it can be assumed that the released protein from tumor cells was associated with TNF (tumor necro-sis factor)-α. Conclusions: Brain tumor cells are active processing cells that they recognize surrounding normal neuron cells, release death factors and induce apoptosis of neuron cells. Released death factors are related toTNF-α.