The invention provides a synthesis method of a budesonide impurity USP-Z1. According to the synthesis method, firstly, budesonide is taken as a raw material and subjected to a reaction with butyryl chloride or butyric anhydride under the condition of an organic solvent and an acid-binding agent to produce a compound USP-Z1-IM1; then, the compound USP-Z1-IM1 is dissolved in the organic solvent, anoxidant is added, oxidation is performed, and the impurity USP-Z1 is produced. The synthesis method adopts a simple process route and is convenient to operate, good in selectivity and high in yield; the synthesized budesonide impurity USP-Z1 can serve as a reference substance for detection and study of budesonide and is applied to quality control of budesonide and related preparations to control the purity of raw materials or preparations of budesonide.