In the present study, hydroxyapatite (HA) /silk fibroin (SF) nanocomposite containing 40 wt % of SF, was synthesized in an aqueous solution of CaCl2/(NH4)2HPO4 system containing SF to mimic bone structure of nano HA crystallites in organic matrix. The experimental results show that SF promotes the preferential growth of nano HA crystallites along the plane (002) which indicates the interaction between nano HA crystallites and SF. The nanocomposite with nano HA crystallites dispersed homogeneously in SF matrix possesses a compression strength of 97.6 MPa higher than that of woven bone. The methodology has a great potential for designing and engineering of biomaterials with improved biological properties. The novel nanocomposite may be used as bone substitutes and tissue engineering scaffolds.