In this study, nonmineralized silk fibroin/gelatin (SF/G) hybrid scaffolds and the mineralized SF/G/hydroxyapatite (SF/G/HA) hybrid scaffolds were fabricated using vacuum freeze-drying method and biomineralization technique. The morphology and mechanical properties of the 2 hybrid scaffolds were characterized. Furthermore, the cytotoxic profiles of the hybrid scaffolds were investigated in vitro by seeding the human osteoblast cells (hFOB1.19). The 2 hybrid scaffolds were both highly porous and the pore sizes of the SF/G as well as SF/G/HA hybrid scaffolds were 260 ± 58 μm and 210 ± 35 μm, respectively. Compared with the SF/G hybrid scaffold, the SF/G/HA hybrid scaffolds exhibited significantly enhanced compressive strength and modulus. Significant early cell adhesion and proliferation on the SF/G hybrid scaffolds were observed, while SF/G/HA hybrid scaffolds effectively improved osteogenic differentiation of hFOB1.19 after 10 days of coculture. The results confirmed that the 2 hybrid scaffolds were both cytocompatible and had almost no negative effects on the hFOB1.19 in vitro. However, the SF/G/HA hybrid scaffolds tended to be more promising for application in bone-tissue engineering with good mechanical property and osteogenic differentiation.