The invention discloses a fusion protein, preparation method thereof and use thereof and belongs to the field of biopharmaceutical technology. The fusion protein according to the present invention has anti-tumor, anti-autoimmune diseases and anti-inflammatory functions ,and therapeutic effects on ophthalmic diseases. According to the long-acting, multifunctional fusion protein of the present invention, the EDSM-Y or EDSM-X polypeptide is fused to the antibody immunoglobulin Fc fragment by a flexible linker so as to obtain the fusion proteins I-V, which can improve the efficacy, prolong the half-life and enhance stability, have characteristics of strong effect, low toxicity and the like, and can be used for the prevention and treatment of solid tumors and various types of inflammation and neovascular ophthalmic diseases. The specific structure of the fusion protein includes: an antiangiogenesis polypeptide, fused to an Fc-related fragment of an immunoglobulin via an intermediate amino acid linker between them. The fusion protein is expressed in a prokaryotic cell or a eukaryotic cell by a genetic engineering method, and the expressed fusion protein is obtained by affinity chromatography.
