Abstract: Copper oxide ore is an important copper resource in China. In recent years, the easily treatable copper minerals have been decreasing annually. Therefore, the efficient enrichment of copper oxide ore is of great significance for copper resources. Due to the fine particle size and high mud content of existing copper oxide ores, it is difficult to separate from gangue minerals. Thus, it is unable to achieve beneficiation indicators using conventional activators for treatment. Based on 2,5−dithiophenol−1,3,4−thiodiazole, a new high−efficiency copper oxide mineral activator, DX−2, was synthesized through a one-pot method. Flotation test results showed that, for the refractory oxidized copper ore with a copper content of 1.23% and an oxidation rate of 90.24%, utilizing DX−2 as the activator, sodium sulfide as the sulfurizer, amyl xanthate and sodium alkyl hydroxamate as collectors, at pH 8, with terpineol as a frother, yielded a copper concentrate with a grade of 18.37% and a recovery rate of 82.59%. These experimental researches introduce a new technical approach for the efficient flotation of refractory copper oxide ores.