Nanofibers show promise as bone tissue engineering scaffolds (BTESs). In this study, electrospun poly (lactic-co-glycolic acid) (PLGA)/silicon nitride (Si 3 N 4 ) composite nanofiber membranes were formed and the osteogenesis capability of mesenchymal stem cells (MSC) from the scaffold marrow was investigated. By modifying the different properties of Si 3 N 4 in the PLGA, two hybrid scaffolds were successfully prepared, including the PLGA/Si 3 N 4 (1 wt.%) nanofiber scaffold and PLGA/Si 3 N 4 (2 wt.%) nanofiber scaffold. The diameter of the fiber nanofiber scaffold PLGA/Si 3 N 4 was decreased and the mechanical strength was increased compared to PLGA. In vitro studies showed better cell adhesion and proliferation on the PLGA/Si 3 N 4 nanofiber scaffold compared to the PLGA nanofiber scaffold. The integration of Si 3 N 4 promoted osteogenesis capacity by increasing the gene expression of bone-related proteins (BMP2, ALP, OPN, COL1a1, Runx2, and OCN), calcium deposits, and support of ALP activity compared to those for the PLGA nanofiber scaffold. Similarly, the PLGA/Si 3 N 4 (2 wt.%) nanofiber scaffold showed better mechanics and biological activity compared to the PLGA/Si 3 N 4 (1 wt.%) nanofiber scaffold. Overall, the PLGA/Si 3 N 4 nanofiber scaffold showed potential as a promising hybrid scaffold for bone regeneration.