The present study was designed to explore the protective effects of Breviscapine (Bre) against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity with cultured PC12 cells and the possible mechanisms involved. The PC12 cells were cultured and exposed to 6-OHDA in the absence or presence of Bre. Its neuroprotective effects in PC12 cells were evaluated by cell viablity, ROS, LDH release assay, intracellular antioxidant enzyme and caspase activities, Nrf2), HO-1 and Bcl-2 family expressions. In the study, we found that Bre might significantly inhibite 6-OHDA-induced oxidative stress in PC12 cells, as indicated by its ability to increase cell viability and inhibit LDH release. The effectiveness of Bre against 6-OHDA-induced oxidative stress may due to restore the intracellular antioxidant defense, thereby reduce ROS production, prevent the development of apoptosis through activating the Nrf2/HO-1 pathways, and reverseing the abnormal expression of Bcl-2 family and caspase, and then alleviating 6-OHDA-induced PC12 cell injury and cell death. © 2015 Taylor & Francis Group, London.