Abstract: Objective： To evaluate the effect of TNF-α on the regulation of the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) through NF-κB signal pathways. Methods：hPDLSCs were isolated and cultured by the method of the limiting dilution technique. hPDLSCs multi-differentiation potential was determined by alizarin Red staining. The gene and protein expression of osteogenic was determined by real-time RT-PCR and Western blot. The expression of NF-κB and osteogenic gene of PDLSCs were determined after treatment by TNF-α (10 ng/mL) by real-time RT-PCR and Western blot. Results：TNF-α inhibits proliferation and differentiation potentials of hPDLSCs. TNF-α upregulated NF-κB protein expression and downregulated Runx2 and Osterix protein levels. Besides, BAY 11-7082 can inhibit the effect of TNF-α. Conclusions： TNF-α regulates the osteogenic differentiation of hPDLSCs through NF-κB signal pathways.