The enhanced role of Interfacial nanobubbles (INBs) in microfine particles flotation is still unclear. In this study, the microfine particles with different sizes were functionalized to obtain different wettability. The temperature difference method was employed to produce the nanobubbles water. Atomic force microscopy (AFM) was utilized to investigate the formation of INBs. A temperature-controlled flotation system was devised to investigate the flotation performance of microfine particles in the presence and absence of INBs. Agglomeration experiments and attachment time tests were conducted to elucidate the enhanced effects of INBs on flotation from the perspectives of particle-particle and bubble-particle interactions. The results showed that both the number and size of INBs increased with the increase of surface hydrophobicity and level of air saturation in water. In the temperature-controlled flotation system, the flotation recovery and flotation rate of microfine particles were improved significantly in nanobubbles water compared to that in normal water. The optimal flotation result of −38 μm strongly hydrophobic particles was obtained in nanobubbles water at 25 ℃. The enhanced impact of INBs on flotation was more pronounced for more hydrophobic particles. The increase in the apparent size of particles and reduction in particle-bubble attachment time facilitated by INBs contributed to the flotation performance of microfine particles. This study underscores the pivotal effect of INBs on the flotation of microfine particles through enhancing particle-particle and bubble-particle interactions.