Aim To investigate the neuroprotective e ffect of echinacoside, one of the phenylethanoids isolated from Cistanche salsa, on tumor necrosis factor-alpha (TNFα)-induced apoptosis in SH-SY5Y neuronal cells. Methods Cell viability was analyzed using MTT assay. Apoptotic cells were detected using DNA fragmentation and flow cytometric analys is. The level of intracellular reactive oxygen species(ROS) and the potential of mitochondrial membrane were determined by laser scanning confocal microscopy (L SCM). The activity of caspase-3 was measured with microplate spectrofluorometer . Results Treatment of cultured SH-SY5Y cells with 100 μg· L -1 TNFα for 36 h induced a significant decrease of cell viability, and t he percentage of apoptosis increased to 37%. The level of intracellular ROS and activity of caspase-3 enhanced, and the red/green ratios of mitochondrial membr ane decreased to 0.35 from 5.97. However, simultaneous treatment with echinac oside (1, 10, or 100 mg·L -1) exhibited cytoprotective effects, reduced fo rmation of the DNA ladder, prevented the accumulation of ROS and caspase-3, reconverted the potential of mitochondrial membrane, and the percentage of apoptosis/necrosis neurons was significantly decreased to 25.9%, 18.3% and 8.2% in a dose-dependent manner . Conclusion These results demonstrate that echinacoside has the neuroprotective capacity to antagonize TNFα-induced apoptosi s in SH-SY5Y cells. The antiapoptotic action of echinacoside may be partially d ependent on an anti-oxidative stress effects, inhibition of caspase-3 activity , and maintain of mitochondria function.