The invention discloses a simulated retrovirus of a targeting tumor; the simulated retrovirus adopts fusion polypeptide consisting of poly-D-lysine and RGD peptide as a genomic vector, packs siRNA retrovirus recombinant and expression vector of gene which is related to the tumor and is formed by self-assembling; a preparation method thereof comprises three steps of the preparation of the fusion polypeptide, the preparation of the siRNA retrovirus recombinant and expression vector and the preparation of the simulated retrovirus; the simulated retrovirus of the targeting tumor of the invention can be targeted and positioned into tumor cells, mediates gene transfection effectively, inhibits the generation and propagation of the tumor obviously, and improves the safety and effectiveness of the tumor gene therapy; and the preparation method is simple and convenient, can be used for preparing anti-tumor drugs and has good application prospect.