In our study we investigated the neuroprotective effects of phenylethanoid glycosides (PhGs) from Cistanches salsa on 1-methyl-4-phenylpyridinium ion (MPP+)-induced apoptosis in cerebellar granule neurons (CGNs). CGNs were treated with 100 μM MPP+ for 24 h to induce apoptosis, simultaneously CGNs were incubated with PhGs at 10, 20 and 40 μg/ml, respectively. In addition CGNs were pretreated with PhGs at 20 μg/ml for 6, 12, 24 h, respectively, and then treated with 100 μM MPP+ for 24 h. 3-(4,5-Dimethylthiazol-2-ylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed that the treatment of CGNs with PhGs inhibited the decrease of cell viability induced by MPP+. The activation of caspase-3 and caspase-8 was induced by MPP+ in apoptosis. The caspase-3 and caspase-8 fluorogenic assays showed that the treatments of CGNs with PhGs efficiently suppressed the activation of caspase-3 and caspase-8 induced by MPP+. It is concluded that PhGs can prevent the MPP+-induced apoptosis in CGNs and exert its anti-apoptosis effect by inhibiting caspase-3 and caspase-8 activities.