The invention discloses a preparation method of a 1,3,5-trisubstituted 1,2,4-triazole compound. The preparation method comprises the following steps that simple substance iodine, tert-butyl hydroperoxide (a 70% aqueous solution), hydrazone and fatty amine are added into organic solvent, the materials are heated to the temperature of 80 DEG C-100 DEG C for a reaction, and after the reaction is complete, aftertreatment is performed to obtain the 1,3,5-trisubstituted 1,2,4-triazole compound. The preparation method has the advantages that the steps are simple, the raw materials are cheap and easy to obtain, and the reaction does not need to be performed under water-free and oxygen-free conditions; in addition, heavy metal does not need to be used as a catalyst, diversely substituted 1,2,4-triazole compounds with different substituted positions can be synthesized through the design, and the applicability of the method is widened while operation is convenient.