The effect of Na2S2O8 on Cu2O surface oxidation and leaching was investigated, and the presence of Na2S2O8 transforms the surface of Cu2O into more easily leachable CuO, resulting in a 35.50% increase in the extraction rate of Cu than that without Na2S2O8. In the acid leaching system, O atoms combined with H+ to form H2O, which was continuously separated from the surface to form vacancies. Cu(I) on the mineral surface formed Cu(0) and Cu(Ⅱ), of which Cu(Ⅱ) separated from the mineral surface and entered the solution, while Cu(0) was reconstructed on the surface, and a Cu-Cu metal bond with a bond length of 2.40 Å was appeared in the DFT calculation, which caused the content of Cu atom on the surface to be higher than that of O atom. After oxidation, high-spin Cu(Ⅱ) contributed by the 3d orbital appeared on the mineral surface. The Cu(Ⅱ) content of the oxidized Cu2O surface was 19.80% higher than that of the pure Cu2O surface, indicating that the copper on the oxidized Cu2O surface was more easily extracted. Moreover, the adsorption energy of chemical adsorption occurring in the presence of oxidant (−1.91 eV) was more negative than that in the absence of oxidant (−0.21 eV).