Cordyceps sinensis has been used as nutritious food and medicine in Chinese society. CS can inhibit tumor growth and induce tumor cell apoptosis. CS induced MA-10 mouse Leydig tumor cell death, but the anti-tumor mechanisms are not fully understood. Thus, the aim of this study was to investigate the apoptotic effect of CS on MA-10 cells and determine the molecular mechanism. CS (2-10 mg/ml) was added to MA-10 cells at different time scales (0-24 h). The condensation of DNA chromatin and apoptotic nuclear fragmentation increased in CS-treated MA-10 cells. Western blot analysis showed that 3 hours of CS treatment caused an increase in caspase-3 and -8 expressions only, which provided further evidence for the involvement of caspase-3 and -8 in CS-induced MA-10-cell apoptosis. CS blocked NF-?B protein expression in a dose-dependent relationship. CS induces MA-10 cell apoptosis by activating caspase-8-dependent and caspase-9-independent pathways and downregulating NF-?B protein expression.