The invention provides a highly-soluble sulbenicillin sodium colon-targeted starch capsule and a preparation method thereof. According to the invention, a starch capsule is used and is filled with sulbenicillin sodium, the nested part of a capsule shell is sealed with a sealing material so as to prepare a hard capsule, and the prepared hard capsule is coated with a colon-soluble coating solution;and the colon-soluble coating solution is prepared by mixing a coating material, a coating solvent and a plasticizer. The invention has the following advantages: the prepared highly-soluble sulbenicillin sodium colon-targeted starch capsule has the triple effects of colon targeting performance, rapid disintegration and slow drug release, prolongs the circulation time of oral sulbenicillin sodium in the body and improves the absorption efficiency of sulbenicillin sodium; compared with the prior art where special colon-soluble capsule shells are selected, the highly-soluble sulbenicillin sodiumcolon-targeted starch capsule of the invention is high in filling percentage, and a coating process adopted in the invention is stable in process, easy to operate and suitable for large-scale industrial production; after coating, the starch hard capsule prepared by using the method can maintain the color and transparency of the original capsule and improve patient compliance; and the preparation method does not need special equipment, and is simple in process, easy to operate and low in cost.