Hydroxyapatite (HA), as a suitable substitutable material for injured bones, attracted much attention because of its chemical and structural similarities to the natural hard tissues. The fluorine (F) is one of the ionic contaminations of biological HA. Addition of F to HA bioceramic increases thermal and chemical stability, and improves mechanical properties when sintered at high temperatures. Furthermore, F stimulates cell attachment, proliferation and differentiation. Nanostructured bulk of fluoridated hydroxyapatite (FHA) is significant for bone tissue regeneration. This material as compared to coarser grain size bulks promotes mechanical properties and biological responses. Therefore, the aim of this work was to fabricate nanostructured FHA bulk via the two-step sintering (TSS) process. Different parameters of the TSS process such as initial and secondary temperatures (T 1 and T 2 ), initial and secondary holding times (t 1 and t 2 ), and compaction pressure (P) were assessed via the Taguchi method. In addition, the effect of F content on sinterability and mechanical properties of FHA was studied. Phase structure, morphology and structure, and functional groups of prepared FHA were characterized using X-ray diffraction (XRD), Scanning Electron Microscopy (SEM) and Fourier Transform Infrared spectroscopy (FT-IR) techniques. Mechanical properties were determined by a microhardness tester and biological properties were evaluated by pH variation and ion releasing in simulated body fluid. P, T 1 , t 1 , and T 2 had the highest effect on consolidation respectively. Mono-phased FHA bulk with high density were produced at 1000 °C, 900 °C, 10 min, 24 hours and 200 MPa for T 1 , T 2 , t 1 , t 2 , and P, respectively which optimized by Taguchi method. The average crystallite sizes of produced FHA were estimated to be 105 nm. By increasing the F content, the sinterability of FHA bulks was decreased and densification was delayed. In addition, hardness increased and fracture toughness decreased as F content increased. Biological evaluation indicated bone-like apatite nucleation and growth on the surface of prepared nanobioceramics. Furthermore, the sintered FHA not only didn’t show any cytotoxicity effect on Human osteoblast cells, although increased their proliferation. As F content increased, Human osteoblast cells proliferation rate a little decreased since the amount of released calcium in the culture medium decreased. Therefore, due to the mechanical and biological improvement, fabricated nanostructured FHA could be a potential candidate for unloaded bone tissue regeneration applications. Keywords : Bioceramic, Fluorapatite, Hydroxyapatite, Two-Step Sintering, Nanostructure, Biocompatibility