Granite-hosted uranium ores exhibit heterogeneous mineral assemblages and complex pore structures, which may restrict lixiviant accessibility and uranium dissolution during acid leaching. This study investigated a mixed nonionic surfactant system comprising OP-10 and Tween 80 for sulfuric acid leaching of a granite-hosted uranium ore containing 787.5 ppm U. Mineralogical characterization, surface-tension measurements, stirred-leaching and column-leaching experiments, and kinetic modeling were conducted to evaluate the leaching performance. The ore was dominated by quartz, feldspar, and other aluminosilicate minerals, with a heterogeneous pore network. OP-10 exhibited a greater surface-tension-reducing ability than Tween 80, and a 3:1 OP-10/Tween 80 volume ratio was selected. In stirred-leaching tests at 30 °C, a liquid-to-solid ratio of 5.0 mL·g⁻¹, and 20 g·L⁻¹ H₂SO₄, uranium recovery after 10 h increased from 72.4% in the H₂SO₄ system to 87.8% in the mixed-surfactant system. Separate kinetic experiments were conducted at 20 °C and a liquid-to-solid ratio of 2.5 mL·g⁻¹. After 31 d of column leaching, cumulative uranium recoveries were 74.0% and 92.6% for the H₂SO₄-only and mixed-surfactant columns, respectively. Nonlinear first-order fitting yielded apparent rate constants of 0.04176 and 0.06480 d⁻¹, respectively. These column results are descriptive observations because only one independent column was tested per condition. Kinetic model comparisons did not establish a unique rate-controlling mechanism, and the possible contributions of interfacial behavior and solution transport remain to be verified. This study provides experimental evidence for evaluating mixed nonionic surfactants in granite-hosted uranium leaching and offers a basis for further optimization of surfactant-assisted leaching conditions for complex hard-rock uranium ores.