The invention belongs to the field of chemical synthesis and particularly relates to a preparation method of 6-fluorine-3-hydroxyl-2-pyrazinamide, which comprises the steps of amidogen protecting, halogen replacing, deprotection and azidation through taking 6-bromine-3-amidogen-2-pyrazinamide as an initial material. The method has the advantages that the material is convenient to purchase and prepare, the method is simple and convenient to operate, the 6-fluorine-3-hydroxyl-2-pyrazinamide prepared by the method has high yield, and the method is applicable to industrial production.