The invention discloses a calycosin derivative and a synthesis method thereof. The derivative is prepared by the steps of: dissolving a compound 1 and a compound 2 in an organic solvent, making the compound 1 and the compound 2 react under a basic condition to obtain an intermediate product 3, and dissolving the intermediate product 3 and a compound 4 in an organic solvent to obtain the targeted crude product. Applicants find that the proliferation of human umbilical vein endothelial cells can be promoted by the derivative of low concentration, so that an effect of good vascular protection isachieved, and therefore the derivative can be applied to the preparation of ERalpha and GPR30 agonists; meanwhile, an inhibitory effect on MCF-7 cells can be generated by the derivative of low concentration (10 uM); the structures of the compound 1, the compound 2, the intermediate product 3 and the compound 4 which are involved in the derivative and the synthesis method of the derivative are shown as follows respectively.