Chemical oxidation is a promising pretreatment method for refractory pyrite enclosure to enhance Au/Ag extraction. Here, persulfate was employed for stepwise oxidation of a refractory pyrite concentrate with encapsulated Au/Ag: (i) pyrite oxidation began with heating-activation persulfate, where hydroxyl radical (•OH) acted as the primary oxidative species for fast-dissolving pyrite into Fe ions; (ii) pyrite self-dissolved Fe ions were in-suit used as a moderate activator of persulfate to generate •OH for sustainable oxidizing pyrite at room temperature. Mineralogical studies have confirmed that oxidation of the sulfide enclosure (FeS2) significantly reduced the particle size of pyrite, accompanied by pores creation and an increase in specific surface area. The variation of microstructure liberated Au and Ag particles to lixiviants for extraction, significantly improving leaching efficiency in an eco-friendly copper(II)-glycine-thiosulfate system to 92.2 % for Au and 88.6 % for Ag, respectively. This work provides a promising process for separating precious metals from refractory pyrite.