The invention discloses a derivative of silybin ethers, and a synthetic method and application thereof. The derivative of the silybin ethers has a structural formula as shown in a formula I, wherein R1 is a -(CH2CH2O)mR4 group; R2 is hydrogen or the -(CH2CH2O)mR4 group; R3 is the hydrogen or the -(CH2CH2O)mR4 group; in the -(CH2CH2O)mR4 group, m is equal to 3, 4, 5, 6, 7 or 8, and R4 is methyl, ethyl, propyl or isopropyl. According to the derivative of the silybin ethers disclosed by the invention, polyethylene glycol oligomers are connected to a C-7 position or a C-7 and C-20 position or a C-3, C-7 and C-20 position of silybin through an ether forming reaction, the solubility of the silybin in water is greatly improved, and a higher fat-water distribution ratio is maintained. Synthetic process conditions are mild, the operation is simple, the yield of products is high, the water solubility of the silybin can be effectively improved, and the bioavailability, the drug effect and the effective component concentration of silybin drugs can be greatly improved.