Abstract: This study investigated the optimization of the grinding-flotation process and the mechanism of collector action for a microfine disseminated gold-bearing ore from Guizhou Province, characterized by fine gold particles, a high degree of gold encapsulation, and gangue minerals prone to sliming. The gold grade of this ore is 3.58 g/t. Gold is mainly encapsulated in sulfide minerals, with pyrite and arsenopyrite being the principal gold-bearing minerals. Gangue contains a relatively high proportion of carbonate and mica minerals prone to sliming, making it difficult to achieve efficient gold recovery through conventional flotation. A suitable process flowsheet was selected through comparative tests. Key factors, including grinding fineness, copper sulfate activator dosage, and the collector regime, were systematically optimized using single-factor tests. A closed-circuit test of the entire process was conducted to verify its stability. The enhancement mechanism of the compound collector was revealed by means of contact angle and surface tension measurements. The results show that the staged grinding and flotation process can progressively expose encapsulated gold and reduce interference caused by gangue sliming. Under the optimized grinding and reagent conditions, the compound collector DY−4 （ammonium dibutyl dithiophosphate and isoamyl xanthate at a mass ratio of 1∶4） yielded favorable separation results, with a gold concentrate grade of 20.26 g/t and a gold recovery rate of 91.92 %. Mechanistic analysis shows that DY−4 can significantly enhance the surface hydrophobicity of pyrite, effectively reduce pulp surface tension, and improve bubble mineralization through synergistic adsorption. These findings provide an interfacial chemical basis for the recovery of microfine gold-bearing pyrite and offer a reference for the efficient development of similar refractory gold ores.