The interaction between air bubbles and solid surfaces plays important roles in many engineering processes, such as mineral froth flotation. In this work, an atomic force microscope (AFM) bubble probe technique was employed, for the first time, to directly measure the interaction forces between an air bubble and sphalerite mineral surfaces of different hydrophobicity (i.e., sphalerite before/after conditioning treatment) under various hydrodynamic conditions. The direct force measurements demonstrate the critical role of the hydrodynamic force and surface forces in bubble-mineral interaction and attachment, which agree well with the theoretical calculations based on Reynolds lubrication theory and augmented YoungLaplace equation by including the effect of disjoining pressure. The hydrophobic disjoining pressure was found to be stronger for the bubble-water-conditioned sphalerite interaction with a larger hydrophobic decay length, which enables the bubble attachment on conditioned sphalerite at relatively higher bubble approaching velocities than that of unconditioned sphalerite. Increasing the salt concentration (i.e., NaCl, CaCl2) leads to weakened electrical double layer force and thereby facilitates the bubblemineral attachment, which follows the classical Derjaguin-Landau-Verwey-Overbeek (DLVO) theory by including the effects of hydrophobic interaction. The results provide insights into the basic understanding of the interaction mechanism between bubbles and minerals at nanoscale in froth flotation processes, and the methodology on probing the interaction forces of air bubble and sphalerite surfaces in this work can be extended to many other mineral and particle systems.