Chitosan, a natural polymer, is a biomaterial which is known to be osteoconductive but lacking in mechanical strength. In this work, to further enhance the mechanical property and biocompatibility of chitosan, we combined it with both chondroitin sulfate, a natural glycosaminoglycan found in bone, and nano-SiO2. The composite scaffold of chitosan/chondroitin sulfate/nano-SiO2 was fabricated by lyophilization. The nanocomposite scaffold showed enhanced porosity, degradation, mechanical integrity, biomineralization and protein adsorption. Biocompatibility and cell attachment-proliferation studies performed using MG-63 cells, advocate its better performance in vitro. To improve the cell seeding efficiency, we coated the scaffold surface with fibrin, which enhanced the initial cell attachment. The cumulative results suggest this novel nanocomposite scaffold to be a suitable candidate for bone tissue engineering.