The calcium phosphate (CaP) particles have attracted much attention in gene therapy. How to construct stable gene particles was the determining factor. In this study,hybrid multi-shell CaP gene particles were successfully constructed. First,CaP nanoparticles served as a core and were coated with DNA for colloidal stabilization. The ξ-potential of DNA-coated CaP nanoparticles was -15 mV. Then polyethylenimine (PEI) was added and adsorbed outside of the DNA layer due to the electrostatic attraction. The ξ-potential of hybrid multi-shell CaP particles was slightly positive. With addition of PEI,the hybrid multi-shell particles could condense DNA effectively,which was de-termined by ethidium bromide (EtBr) exclusion assay. The hybrid particles were spherical and uniform with diameters of about 150 nm at proper conditions. By simple modification of PEI,the hybrid multi-shell CaP gene particles were successfully constructed. They may have great potential in gene therapy.