〔Abstract〕 Objective To observe the protective effect of honokiol(HNK) on hydrogen peroxide(H2O2)-induced injury of human neuroblastoma cells(SH-SY5 Y) and explore its possible mechanism. Methods SH-SY5 Y cells were treated with 400 μmol/L H2O2for 24 hours to establish a cell injury model. In the protection group, SH-SY5 Y cells were preincubated with HNK for 6 hours, and then treated with 400 μmol/L H2O2for 24 hours. The activity of SH-SY5 Y cells was determined by CCK8 colorimetry. Apoptosis of SH-SY5 Y cells was determined by flow cytometry. The protein expressions of cytoplasmic Bcl-2, Bax, caspase-3, BIP, CHOP and caspase-12 were detected by Western blot. Results HNK promoted the activity of SH-SY5 Y cells treated with H2O2(P<0.01), decreased cell apoptosis rate, increased Bcl-2/Bax ratio, and decreased protein expressions of Caspase-3(P<0.05), BIP, CHOP and Caspase-12(P<0.01). Conclusion HNK protects SH-SY5 Y cells from H2O2-induced damage by inhibiting ERS-associated cell apoptosis.