Purpose: This study aimed to determine expressions of hepatocyte growth factor (HGF) and MET proto-oncogene receptor tyrosine kinase (MET) in palatal periosteum (PP) and to examine the effect of HGF/MET on osteogenic differentiation of human palatal periosteum-derived mesenchymal stem cells (PD-MSCs).Methods: HGF/MET proteins in human palatal periosteum (n = 3) were localized using immunohistochemistry. PD-MSCs (n = 3) were cultured in serum-free Essential 8 (E8) medium or osteogenic medium with and without Capmatinib, a selective ATP-inhibitor of MET. HGF concentration in vitro was measured with ELISA. Relative gene expression was quantified from PD-MSCs by quantitative reverse transcription real-time polymerase chain reaction.Results: Immunohistochemistry detected co-localization of HGF and MET protein in PP. HGF protein levels were significantly higher (P < 0.05) in osteogenic media (day 21: 12.19 ± 8.36 ng/mL) than in E8 medium (day 21: 0.42 ± 0.72 ng/mL). MET inhibitor had a limited feedback effect on the expression profile of the osteogenic genes tested. Gene expression levels for all but three genes were comparable in serum-free and osteogenic media at all time points.Conclusion: HGF/MET present in human PP and HGF is upregulated in vitro during osteogenesis; however the targeted pathways controlled by MET may not involve osteoblast maturation.