The invention relates to a tilmicosin soluble powder. The tilmicosin soluble powder is characterized by comprising the following ingredients in percentage by mass: 5-25% of tilmicosin, 3-15% of a cosolvent, 1-3% of a solubilizer, 3-8% of PEG and filler. The invention further provides a preparation method of the tilmicosin soluble powder. According to the tilmicosin soluble powder and the preparation method thereof disclosed by the invention, the preparation process is simple, only simple mixing is needed, the raw materials are all commercially available, low in price and easily available, and the obtained compound preparation is stable in performance; because of addition of the cosolvent and the solubilizer, the tilmicosin soluble powder is good in dissolving property, quite suitable for applications in clinic aspects, capable of meeting the relevant provisions of pharmacopoeia, suitable for industrialized large-scale production, and quite wide in application prospect. The tilmicosin soluble powder has a high practical value.