Liver regeneration is a vital process of recovery after liver damage, which is a promising clinical strategy after partial hepatectomy (PHx). Schisandrol B (SolB), one of the bioactive ingredients from Schisandra sphenanthera, displays significant hepato-protection effects against drug-induced liver injure in mice. However, the effect of SolB on liver regeneration after PHx remains unclear. Here, we showed that SolB treatment promoted liver mass restoration and increased the number of proliferative hepatocytes following PHx. SolB treatment significantly improved the levels of growth factors (HGF and EGF) and cytokines (IL-6), which further activated STAT3/Akt/MAPK signaling pathways and induced the expression of several the protein of cell cycle core. Overall, this study is the first to demonstrate the role of SolB in promoting liver regeneration during PHx challenge, which provide a clinically relevant argument for using SolB to facilitate liver recovery after undergoing PHx or liver transplantation.