The strontium-substituted hydroxyapatite (SrHA) is a commonly used material in bone regeneration for its good osteoconductivity and high alkaline phosphatase (ALP) activity. Scaffolds used in bone defects require a high compressive modulus. However, the SrHA nanoparticle-doped scaffold cannot properly fit the required mechanical properties. Therefore, a lot of effort has been used to fabricate synthetic bone scaffolds with biocompatibility, suitable mechanical properties, antibacterial ability and osteoconductivity. Here, we used a facile hydrothermal method to synthesize graphene oxide (GO)-reinforced SrHA nanoparticles. The incorporation of GO can be used as nucleation and growth active sites of hydroxyapatite. In addition, GO is easy to self-assemble into a layered structure in the dispersion, which can effectively regulate the deposition of hydroxyapatite on the surface of GO. The scaffold was fabricated using a freeze-drying method by incorporating SrHA/GO nanoparticles into chitosan (CS) and quaternized chitosan (QCS) mixed solutions. The compressive modulus of the CS/QCS/SrHA/GO scaffold reached 438.5 kPa, which was 4-fold higher than that of the CS/QCS scaffold. The CS/QCS/SrHA/GO scaffold exhibited significantly higher in vitro mineralization levels and ALP activity. In vivo rat skull repair indicated that the CS/QCS/SrHA/GO scaffold had a significant role in promoting bone regeneration. This study provides a new strategy for modifying hydroxyapatite to satisfy the biomedical demand of bone tissue engineering scaffolds.