The invention discloses a preparation method of a 3,4,5-trisubstituted 1,2,4-triazole compound. The preparation method comprises the following steps: adding aryl ethanone and iodine into dimethyl sulfoxide, conducting heating to 90-110 DEG C, performing reacting for 4-6 hours, adding iodine, sodium dihydrogen phosphate, pyridine and trifluoroethyl imine hydrazide into the organic solution, carrying out heating to 110-130 DEG C, performing reacting for 12-20 hours, and after the reaction is completed, carrying out post-treatment to obtain the 3,4,5-trisubstituted 1,2,4-triazole compound. The preparation method is simple to operate, the initial raw materials are cheap and easy to obtain, the reaction does not need to be carried out under anhydrous and anaerobic conditions, heavy metal does not need to be used as a catalyst, the reaction can be easily expanded to gram level, operation is convenient, and the applicability of the method is widened.