Cyclooxygenases (COX) appear to be involved in the mechanism of apoptosis in various cancer cells. In this study we investigated the role of COX in the capsaicin (Cap)-induced apoptosis in SK-N-SH human neuroblastoma cells. Cap induced decreased cell viability and apoptosis in a dose-dependent manner. Cap also significantly reduced the basal generation of reactive oxygen species (ROS) and lipid peroxidation in a time-dependent fashion. Cap markedly suppressed the expression of COX-1 and COX-2. Pretreatment with NS-398, a selective COX-2 inhibitor, or indomethacin, a nonselective COX inhibitor, significantly enhanced the Cap-induced decreased cell viability and apoptosis. Exogenous application of an oxidant, H2O2, significantly prevented the Cap-induced apoptosis and suppressed the expression of COX isoforms. These results suggest that redox status-dependent regulation of COX expression may mediate apoptosis induced by Cap in human neuroblastoma cells.