Abstract: Generally, the flotation performance of mineral particles in a wide size range is usually poor, which can be attributed to the high reagent consumptions and low floatability differences between valuable and gangue minerals. Classification flotation is an effective method for improving the flotation efficiency of particles in a wide size range and is commonly used for coal slime. However, for refractory iron ores, the literature on the relative technology and basic theory of classification flotation, which are necessary and beneficial for the effective utilization of refractory iron ore resources, is scarce. In this study, flotation tests, DLVO theory calculations, and focused beam reflectance measurement (FBRM) particle size analysis were used to analyze the effect of particle size distribution on the flotation separation of hematite and quartz in the sodium oleate system. The flotation results of artificial mixtures show that the flotation performance of coarse or medium hematite–quartz mixture (such as CH&CQ and MH&CQ) with a narrow size range is better than that of the wide size range mixtures. The separation efficiency of CH&CQ and MH&CQ is 85.49% and 84.26%, respectively, which is higher than that of the wide size range mixtures (74.94%). However, the separation efficiency of fine hematite–quartz mixture with a narrow size range (FH&FQ) decreases to 54.98%. The flotation kinetic tests demonstrate that the flotation rate and recovery of hematite are not only related to the particle size of hematite but also influenced by the particle size of quartz. The fine quartz particles could reduce the hematite flotation rate and recovery. The DLVO theory calculations demonstrate that the interaction energies between hematite and quartz are repulsive, indicating that fine quartz particles scarcely cover the hematite surface to depress floatability, which is consistent with the FBRM results. The bubble–particle collision analysis indicates that the collision between hematite and bubbles might be influenced by the “boundary layer” effects of fine quartz particles, resulting in the decreased bubble–particle efficiency of collision and attachment, which may explain the decrease in hematite flotation rate and recovery.