Objective：To study the protective effect and possible mechanism of silibinin on cell damage of SH-SY5Y induced by hydrogen peroxide（H2O2）. Methods：SH-SY5Y cell damage model was established by H2O2 in vitro. After pretreatment with silibinin，the cell viability was determined by MTT，reactive oxygen species（ROS），apoptosis and mitochondrial membrane potential（MMP）were determined by flow cytometry，and the expressions of Cleaved-Caspase-9 and Cleaved-Caspase-3 were detected by Western blot. Results：Compared to the model group，pretreatment with 50 μmol/L and 100 μmol/L silibinin for 3 h attenuated the damage of SH-SY5Y cells treated with H2O2，improved the cell survival rate（P＜0.05），reduced the apoptosis rates（P＜0.05）and the release of ROS，stabilized MMP（P＜0.01），decreased the expression of Cleaved-Caspase-9 and Cleaved-Caspase-3. Conclusion：Silibinin can protect SH-SY5Y cell from H2O2，which may be related to its antioxidant capacity，protection of mitochondrial membrane potential，and reduction of the expression of Cleaved-Caspase-9 and Cleaved-Caspase-3.