This study observed whether the silk fibroin/poly lactic-co-glycolic acid (SF/PLGA) nanofiber membrane three-dimensionally coated with porous calcium phosphate-based composite can promote the proliferation of osteoblasts, thereby improving osteoporosis. The SF/PLGA nanofiber membrane was used to three-dimensionally coated with the porous calcium phosphate-based composite to analyze proliferation of osteoblasts, hFOB1.19 expressions by Western blot, activity change of hFOB1.19 by CCK-8 assay. The morphology was observed with an electron microscope. Alizarin Red staining showed that the SF/PLGA nanofiber membrane three-dimensionally coated with porous calcium phosphatebased composite promoted osteogenic differentiation and upregulated the expression of osteogenic related genes. It inhibited adipogenic differentiation and the expression of adipogenic genes. SF/PLGA composite material promoted the viability of osteoblasts hFOB1.19, upregulatedGLUT3, downregulated the expression of various apoptosis-related proteins in hFOB1.19. SF/PLGA composite material can reduce the apoptosis efficiency of osteoblasts, promote the proliferation of osteoblasts, and inhibit apoptosis, thereby improving osteoporosis.