In this study, a novel organic depressant maleyl 5-amino-1,3,4-thiadiazole-2-thiol (MATT) was synthesized and utilized as a galena depressant in the flotation separation of molybdenite and galena. The results of the flotation test indicated that MATT exhibited an excellent depression ability on galena but barely influenced the flotation of molybdenite in the pH range of 6.0–11.0. Zeta potential results suggested that MATT preferentially adsorbed on galena surface. UV-visible spectroscopy analysis indicated that the stoichiometric ratio of lead ion and reagent in the complex compound. XPS analysis demonstrated that the S (-SH) atom and N (1,3,4-thiadiazole group) atom of MATT coordinated with the Pb atom on galena surface.