Autogenous bone and metallic implant grafting has been used to repair and regenerate bone defects. However, there are still many unresolved problems. It is suggested that bioceramic nanoparticles should be developed and designed to promote effective bone regeneration. In addition, it is necessary to synthesize bioceramic nanoparticles that can support proteins related to bone repair and regeneration such as collagen and albumin. As the protein-interactive bioceramic, hydroxyapatite (HA) deserves to be mentioned and has several attractive properties that are useful in biomedical fields (e.g., biocompatibility, protein adsorption capacity and stability in the physiological environment). In order to prepare novel HA nanoparticles with high biocompatibility, it can be considered that human bones are mainly composed of HA and contain a small amount of silicate, and therefore, the design of coexistence of HA with silicate can be focused. Moreover, it is proposed that the state of the hydration layer on the nanoparticle surfaces can be controlled by introducing heteroelements and polymer chains, which have a great influence on the subsequent protein adsorption and cell adhesion. In this perspective, in order to develop novel bioceramic nanoparticles for the treatment of bone defect, the design of highly biocompatible HA nanoparticles and the control of the hydration layer and protein adsorption states on the surfaces were systematically discussed based on their surface modification techniques, which are very important for the proper understanding of the interface between cells and bioceramics, leading to the further application in biomedical fields.