Objective：To investigate the effect of activation of alpha 7 nicotinic acetylcholine receptors（α7-nAChRs）combined with calcium ion（Ca²⁺ ）on the odontogenic/osteogenic differentiation of lipopolysaccharide（LPS）-stimulated human dental pulp stem cells （DPSCs）. Methods：DPSCs were isolated and cultured，and surface marker expression of DPSCs was identified by flow cytometry. The effect of α7-nAChRs agonist PNU-282987 and Ca²⁺ on DPSCs proliferation were detected by CCK-8. The optimal concentration of PNU- 282987 to promote alkaline phosphatase（ALP）activity in DPSCs was determined through ALP activity and staining. E.coli lipoplysaccharide（LPS）was used to simulate inflammatory microenvironment stimulation of DPSCs. The expression of proteins：type Ⅰ collagen（COL-I），dentin sialoprotein（DSPP），osteopontin（OPN），ALP，runt-related transcription factor2（RUNX2），osterix（OSX）， as well as the gene expression（COL-I，DSPP，OPN，ALP，RUNX2，OSX）and mineralized matrix related to odontogenic/osteogenic differentiation was examined by Western blot，quantitative real-time polymerase chain reaction（RT-qPCR）and Alizarin red staining.Fura-2 AM was used to detect intracellular Ca²⁺ flux. Results：The CCK-8 assay showed that PNU-282987 at a concentration of less than 10 μmol/L had no inhibitory effect on cell proliferation，and this concentration significantly increased ALP activity in LPS-stimulated DPSCs. Ca²⁺ at a concentration of less than 2 mmol/L had no inhibitory effect on cell proliferation；Western blot and RT-qPCR experiments showed that the expression of osteogenic/osteogenic related proteins（COL-I，DSPP，OPN，ALP，RUNX2，OSX）， genes（COL-I，DSPP，OPN，ALP，RUNX2，OSX），and mineralized matrix formation in LPS-stimulated DPSCs were significantly upregulated after treated with PNU-282987 and Ca²⁺ ，with the most significant upregulation observed when the two were combined（P < 0.001）. Fura-2 AM Ca²⁺ probe results revealed an increase in intracellular Ca²⁺ in DPSCs. Conclusion：10 μmol/L PNU-282987 combined with 2 mmol/L Ca²⁺ can promote the odontogenic/osteogenic differentiation of LPS-stimulated DPSCs.