Over the past few years, efforts in developing efficient non-viral carriers for the intracellular delivery of siRNA have become increasingly intensive, due to the great potentials exhibited by siRNA-mediated gene silencing. Major challenges existing in the research field of non-viral siRNA delivery are to develop safe and cost effective delivery systems. Calcium phosphate (CaP) is known to be biocompatible and non-cytotoxic. Hence, it could be a promising candidate material for the fabrication of siRNA delivery systems. Here we report a facile method to prepare PEGylated CaP/siRNA nanoparticles (NPs) by taking advantage of electrostatic interactions between the anionic charges of siRNA and the cationic charges on the CaP crystal surface. Physicochemical characterization of the resulting NPs reveals that the NPs exhibit a particle size between 90-200 nm, depending on preparation conditions. Detailed investigations were carried out regarding the effect of preparation parameters (i.e., pH value of precursor buffer, phosphate salt, poly(ethylene glycol) molecular weight) on the physicochemical and biological properties. The results show that under optimized preparation conditions, significant gene silencing efficiency was achieved on cultured cells.