Desfluraneis a widely-used general anesthetics. However, recent reports showed its significant side effect in the nervous system. Desflurane could lead to the neuronal death and affect the working memory. Unfortunately, the mechanism underlying the action of desflurane is still not clear and there is still no potent medicine to prevent the lesion in the central nervous system caused by general anesthetics. In this study, we found α-lipoic acid, an antioxidant exerting protective effect on multiple cells tissues, could resist the neurotoxicity caused by desflurane exposure. Lipoic acid possessed strong anti-apoptotic effect on the desflurane-treated hippocampal neurons, which was mediated by the Caspase-3 dependent pathway and NF-kappaB signaling. Collectively, we found a promising candidate to be clinically applied in intervention against the damage in nervous system by the desflurane.