In this study HYDROXYAPATITE (HA), flour-HYDROXYAPATITE (FHA) and fluorapatite (FA) nanopowders synthesized by sol-gel route. Theses powders are used as biocompatible materials for bone replacement and teeth restoration. Ammonium fluoride (NH4F MERK), calcium nitrate [Ca(NO3)2,4H2O MERK] and triethyl phosphite [TEP, (C2H5O) 3P MERK)] were used as F, Ca and P precursors respectively. Triethyl phosphite was first hydrolyzed in ethanol with a small amount of distilled water. To prepare FHA and FA, an appropriate amount of the NH4F powder was added directly to TEP solution. The appropriate amounts of TEP solution was added dropwise to the calcium nitrate solution to yield a stoichiometric ratio of Ca/P=1.67. The resulted solution stirred for 1 h and aged at 25°C for 24 h and 40°C for 72h afterward. After oven drying at 80°C, the powder samples were heat-treated at 550°C for 1 h in air. Microstructural characteristics, powder morphology, chemical structure and phase analysis and in vitro study were performed by Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), X-Ray Diffraction (XRD), Fourier Transform Infra-Red (FTIR), Zetasizer instrument and cell culture method. Fluoride-substituted HYDROXYAPATITE powders (FHA) and Fluor apatite (FA) were successfully fabricated via a sol–gel technique with the incorporation of different levels of fluoride ions. Nearly complete substitution of the OH¯ by F¯ occurred with heat treatment, which was confirmed by FTIR analysis. The particle size distribution of powders evaluated by a zeta-sizer instrument was 100-160nm. The XRD results showed that the crystal size of powders is 20-50nm. The phase stability and crystallinity were different depending on the level of fluoride substitution. Moreover, the crystallinity and crystallite size of the powders increased with fluoride substitution. These improvements in the crystallization and phase stability of the apatite structure, resulting from the fluoride substitution via the sol– gel process, suggest enhanced performance of the FHA powders. The cellular response to the HA, FHA and FA powder was assessed by an in vitro culture method using fibroblastic L929 cells. After culturing for 3 days, the results showed that the number of cells increased with increasing fluoride substitution.