To observe the effects of tanshinone IIA (Tan IIA) on the neurotoxicity induced by ethanol in PC12 cells and to explore its protective role. PC12 cell survival was measured by MTT assay. The formation of reactive oxygen species (ROS) and lactate dehydrogenase (LDH) release were detected by 2',7'-dichlorofluorescin (DCF) fluorescence and calorimetric method, respectively. The percentage of cell apoptosis was monitored by flow cytometry. The expression of p53 was detected by immuno-fluorescence and flow cytometry. Ethanol significantly impaired the survival of PC12 cells as demonstrated by MTT assay. Ethanol also induced significant ROS formation and increased LDH release. Pre-incubation with Tan IIA in the culture medium significantly reversed these changes. Ethanol caused cell apoptosis and the upregulation of p53 protein. The anti-apoptosis effects of Tan IIA on ethanol-induced toxicity were accompanied by the downregulation of pro-apoptotic p53 protein expression. Tan IIA can protect neurons from apoptosis and might serve as a potential therapeutic drug for neurological disorders induced by ethanol.