The invention discloses a preparation method of cefazedone. A starting material 7-amino acetoxyl-removed cepham acid (II) reacts with 3,5-dichloro pyridone acetate (III) to prepare a compound IV, the compound IV performs substitution reaction to obtain a compound V, the compound V reacts with 2-sulfydryl-5-methyl-1,3,4-thiadiazole to obtain a final product cefazedone. The cheap starting material reacts with a condensing agent, the reaction process is controllable, the operation is simple, the purity and the yield are high, and the method is suitable for industrial production.