Objectives: NF-κB signaling pathway plays a complicated role in the biological functions of mesenchymal stem cells.However, the effects of NF-κB pathway on the odonto/osteogenic differentiation of stem cells from apical papilla (SCAPs) remain unclear.The present study was designed to evaluate the effects of NF-κB pathway on the osteo/odontogenic capacity of SCAPs in vitro.Methods: SCAPs were isolated and purified from human immature root apex.Flow cytometric analysis was conducted to identify SCAPs.NF-κB pathway in stem cells was respectively activated and blocked by using TNF-α and BMS-345541 (a selective inhibitor of IKK).Then the proliferation and osteo/odontogenic differentiation of treated SCAPs were subsequently investigated.Result: Western blot results demonstrated that NF-κB pathway in SCAPs was successfully activated by TNF-α (10 ng/mL) or blocked by BM8-345541 (1 μmol/L).NF-κB pathway-activated SCAPs presented a higher proliferation activity compared with control groups, as indicated by dimethyl-thiazol-diphe-nyl tetrazolium bromide assay (MTT) and flow cytometry assay (FCM).Wound scratch assay revealed that NFκB pathway-activated SCAPs presented an improved migration capacity, enhanced alkaline phosphatase (ALP) activity and upregulated mineralization capacity of SCAPs, as compared with control groups.Meanwhile, the odonto/osteogenic markers (ALP/ALP, RUNX2/RUNX2, OSX/OSX, OCN/OCN, OPN/ OPN, BSP/BSP, DSPP/DSP, DMP-1/DMP-1)in NF-κB pathway-activated SCAPs were also significantly upregulated as compared with control groups at both protein and mRNA levels.However, NF-κB pathway inhibited SCAPs exhibited a lower proliferation/migration capacity, and decreased odonto/osteogenic ability in comparison with control groups.Conclusions: Our findings suggest that NF-κB pathway plays a paramount role in the proliferation and committed differentiation of SCAPs.