The present disclosure discloses preparation and use of sugar-targeting nanoparticles for modifying siRNA. A sugar-targeting nanoparticle, including targeting nanocarriers, wherein the targeting nanocarriers are formed by linking in sequence a targeting molecule, a first linking compound, a first hydrophilic biomaterial, a second linking compound and a cationic compound through chemical bonds; the first linking compound and the second linking compound both have a carboxyl group; the first linking compound has a maleimido group at the same time, and the targeting molecule is a cycloaldohexose. Providing the cycloaldohexose as the targeting molecule facilitates the nanoparticles targeting the GLUT-1 protein on the capillary endothelial cell membrane on the blood brain barrier, and the nanoparticles are transferred to the brain with high efficiency through the effect of the GLUT-1 protein to transport cycloaldohexose, thereby effectively penetrating the blood brain barrier, and helping to improve the efficiency of sugar-targeting nanoparticles penetrating the BBB.