Fluidized-bed flotation is a novel process with combined features of flotation and density separation. The application of fluidized-bed flotation in grinding circuit to reject coarse gangues for sulfide ores has been increasingly attracting attentions. Previous studies have focused on the effect of mineral liberation on coarse particle separation. Little work has yet been conducted to simultaneously investigate the effect of mineral liberation, particle and bubble sizes on the fluidized-bed flotation efficiency. The lack of this work has hindered the process optimization to some extent. In this study, three sizes of bubbles (498 μm, 1200 μm, 1952 μm) were generated to separate molybdenite ores under three particle size fractions (150–450 μm, 450–700 μm and 700–1000 μm) in a fluidized-bed flotation column (80 mm in diameter). For the 150–450 μm and 450–700 μm particles, small bubbles of 498 μm could achieve separation by effectively reducing the particle density. For the 700–1000 μm particles with greater mass, intermediate bubble of 1200 μm was required to reduce the particle density for separation. No separation was observed for the three particle size classes with the oversized bubbles of 1952 μm due to high bubble detachment probability. It was concluded that fluidized-bed flotation is a consequence of matched bubble and particle sizes affected by the exposure rate of hydrophobic mineral and its distributing discreteness, the underlying mechanism for which was discussed. It is believed that the outcomes of this work could facilitate the optimization of fluidized-bed flotation in coarse gangue rejecting for sulfide ores.