We investigate the role of depletion interactions in the particle-bubble interactions that determine the attachment capability of particles on the bubble surface in flotation. In this article, we propose a theoretical model that explains how this attractive interaction could enhance flotation efficiency. Two optimum conditions are determined for the concentration and molecular weight of the depletion agent. The optimum concentration can be determined through the extent of surface activity of the depletion agents. The magnitude of the depletion attraction increases as the concentration increases; however, an increase in the concentration simultaneously enhances its surface concentration. The bubble surface adsorption of the depletion agent results in polymer brushes on the bubble surface that produce a large repulsive interaction. In contrast, the optimal molecular weight of the depletion agents is given by the interaction between the depletion agent sizes, which is determined by its molecular weight and Debye length which is determined by the solution ionic strength. We demonstrate that exploiting this depletion interaction could significantly enhance the flotation efficiency and in principal could be used for any particle system.