Oxidative stress, due to the excessive production of ROS (reactive oxygen species), is one of the main reasons for the development of AD (Alzheimer's disease). More and more evidence shows that oxidative stress damage impairs the physiological function of nerve cells by inducing apoptosis. To find a candidate drug that can effectively protect neurons from oxidative stress injury may have therapeutic potential for the AD. In this study, we tested the neuroprotective effect of artemisinin, an FDA-approved antimalarial drug, on oxidative damage of PC12 cells induced by hydrogen peroxide and its related mechanisms. It was found that artemisinin reduced the cell viability loss of H2O2 in PC12 cells. In addition, flow cytometry showed that artemisinin could significantly reduce the apoptosis of PC12 cells induced by H2O2. In addition, Western blot analysis showed that artemisinin stimulated p38MAPK signal transduction, and treatment of PC12 cells with specific p38MAPK pathway inhibitor SB203580 blocked the neuroprotective effect of artemisinin. These results suggest that artemisinin is a potential protective agent, which protects PC12 cells from H2O2 damage by activating the p38MAPK pathway.