Objective To study the protective effects of genistein (Gen) on the apoptosis of PC12 cells induced by beta amyloid 25-35 (Aβ 25-35) and its possible mechanism. Method PC12 cells were divided into control group, Aβ 25-35 group, and 3 Gen groups (at the dosage of 25, 50 and 100 μmol/L). After pre-incubated with or without Gen for 2 h, PC12 cells were exposed to 20μmol of Aβ 25-35 for 24 h. The relative expression of β-actin, caspase-3, caspase-9, bad, bcl-xl and LRP5 mRNA in PC12 cells were analyzed by RT-PCR. Results Compared with the Aβ treated group, the expression of caspase-3, caspase-9 and bad mRNA were significantly decreased (P < 0.05), but the expression of bcl-xl, LRP5 mRNA were significantly increased ( P < 0.05) in the high dose Gen group. Conclusion The neuroprotection of Gen on PC12 cells against apoptosis induced by Aβ 25-35 might be the effect of down-regulating the expression of caspase-9, caspase-3 and bad mRNA, and up-regulating the expression of bcl-xl, LRP5 mRNA.