In this study, we employed a synergistic process combining alkaline leaching pretreatment with mixed acid leaching to purify quartz sand and efficiently eliminate metallic impurities. First, systematic single-factor optimization was used to determine the optimal alkaline leaching parameters to be a NaOH concentration of 8%, a reaction time of 2 h, and a temperature of 225℃. After alkaline leaching, a porous and loose structure was formed on the quartz surface, along with a large number of cracks and pits, which significantly enhanced the mass transfer efficiency of the subsequent acid leaching. Based on this, a ternary mixed acid system (H₃PO₄-H₂SO₄-H₂C₂O₄) was used for pressure leaching. The acid leaching process parameters were optimized using response surface methodology, which determined the optimal conditions to be a temperature of 249℃, a solid–liquid ratio of 1:5, and a time of 6 h. After treating the quartz sand with the combined process, the sand’s total metallic impurity content was significantly reduced from the initial 523.2 mg/kg to 82.6 mg/kg, which amounts to an overall removal rate of as high as 84.33%. The contents of Al, Ca, Fe, K, Mg, Na, and Ti were 50.4, 8.1, 2.2, 6.9, 2.3, 11.5, and 1.2 mg/kg, respectively.