A method for preparing sulfobutyl ether-β-cyclodextrin. β-cyclodextrin and 1,4-sulfobutyrolactone are used as raw materials, and a proper amount of an organic solvent is introduced into an alkaline aqueous solution, so that the solubility of the 1,4-sulfobutyrolactone is increased, and the synthesis yield of the sulfobutyl ether-β-cyclodextrin is improved. Operations including ultrasonic dialysis, active carbon decoloration, freeze-drying and so on are performed on the obtained product solution, so as to obtain a powder product of the sulfobutyl ether-beta-cyclodextrin.