The invention belongs to the field of medicine and chemical industry and discloses a synthesis method of topiroxostat. The method comprises that 4-cyanopyridine as a starting raw material is oxidized by hydrogen peroxide to form an intermediate 1, the intermediate 1, sodium methoxide and ammonium chloride undergo a reaction to produce an intermediate 2, the intermediate 2 and 4-cyanopyridine undergo an annulation reaction under action of cuprous bromide and sodium carbonate to produce an intermediate 3, and the intermediate 3 and trimethylsilyl cyanide undergo a cyanation reaction to produce topiroxostat. The method utilizes low-price 4-cyanopyridine as a starting raw material, and in the first reaction step, methanol is used as a solvent and 4-cyanopyridine nitrogen oxide as the intermediate 1 is prepared. The method has a high yield and produces a high-purity product. The whole route is easy to operate and is conducive to industrial mass production.