T riptolide is a natural active compound that has signifi cant neuroprotective properties and shows promising effects in the treatment of A lzheimer's disease (AD).Recent studies have shown that autophagy occurs in AD. In this study, we determined whether autophagy regulated by triptolide ameliorates neuronal death caused by am yloid-Beta 1-42 (Aβ 1-42 ). We examined the effects of triptolide on cell viability, autophagy, apoptosis, and the protein kinase B/mammalian target of the rapamysin/70 kDa ribosomal protein S6 kinase (Akt/mTOR/p70S6K) signaling pathway in PC12 cells. The results indicated that triptolide treatment exhibited a cytoprotective effect against cell injury induced by Aβ 1-42 . Triptolide also reduced apoptosis and enhanced cell survival by decreasing autophagosome accumulation and inducing autophagic degradation. Furthermore, our results also showed that activating the Akt/mTOR/p70S6K mechanism was one reason for the protection of triptolide. Triptolide treatment protected against Aβ 1-42 -induced cytotoxicity by decreasing autophagosome accumulation, and inducing autophagic degradation in PC12 cells. These fi ndings also suggest that the reduction of autophagosome accumulation observed in triptolide-treated cells was Akt/mTOR/ p70S6K pathway dependent. Overall, triptolide exhibits a neuron protective effect and this study provides new insight into AD prevention and treatment.