The invention discloses a posaconazole freeze-dried powder injection and a preparation method thereof. The powder injection comprises an active therapeutic ingredient of posaconazole, a solubilizer of cyclodextrin and a pH conditioning agent. An acid is added in preparation processes to form a salt for solubilization. A mixed solvent comprising an organic solvent and injection water is employed, wherein the concentration of posaconazole in the mixed solvent is 2.5 to 15g / ml, the organic solvent is 3.0 to 10.0% by volume, and the balance is the injection water. In the preparation processes, the posaconazole and the acid are stirred or mixed, the organic solvent is added, the mixture is heated stirred or ultrasonically treated to be uniform, the cyclodextrin solution is added, mixture is stirred to be a clear solution, the pH value of the mixture is adjusted, the injection water is added to a constant volume, pyrogens are removed, and then aseptic filtration, subpackaging and freeze-drying are performed. The posaconazole freeze-dried powder injection of the invention has advantages that: the content of the active therapeutic ingredient is high, the stability is excellent, the powder injection is convenient for transport and storage, and the application of the posaconazole in the field of preparations is expanded.