Objective：To explore the protective mechanism of curcumin（Cur）on the hippocampal neurons of mice injured by okadaic acid（OA），and to provide a new theoretical basis for the treatment of Alzheimer’s disease. Methods：Mouse hippocampal neuron HT-22 cells were treated with OA，and divided into four groups：control group，Cur group，OA group，and OA+Cur group. The cell viability was measured by MTT assay. The apoptosis was detected by using Annexin V-FITC/PI double staining fluorescence microscope and flow cytometry. DCFH-DA probe fluorescence microscopy and flow cytometry were used to determine the intracellular reactive oxygen species（ROS）production，and Western blot was used to detect the levels of cleaved-caspase-3，Bcl-2，total Tau（t-Tau），and phosphorylated Tau（p-Tau）proteins. Results：Compared with the control group，the cell viability decreased in a dose-dependent manner after HT-22 cells were treated with different concentrations of OA for 24 hours，and the difference was statistically significant. When OA injury lasted for a certain period of time，the level of ROS in the cells increased. OA injury promoted cell apoptosis，reduced expression of anti-apoptotic protein Bcl-2，increased expression of cleaved-caspase-3 protein，and the expression of t-Tau and p-Tau protein increased abnormally. Compared with the OA group，the cell viability increased，the apoptosis rate and the production of ROS decreased in the OA+Cur group，meanwhile，the expression of Bcl-2 protein increased，whereas the expressions of cleaved-caspase-3 protein，t-Tau and p-Tau decreased. Conclusion：Curcumin can protect hippocampal neurons from OA injury in mice. The present results provide a new theoretical basis for the protection of Alzheimer’s disease-related neurons.