The particle interaction behavior is important in flotation process, and the interaction energy calculation is helpful for evaluating this behavior. This study investigates and compares the floatability of magnesite, dolomite, and quartz in single mineral flotation and artificial mixture flotation with dodecylamine (DDA) as collector. The results showed that while the pH, dissolved ions, and competitive adsorption had a minor influence on their floatability, fine magnesite and dolomite largely decreased the recovery of quartz. Scanning electron microscope (SEM) analysis on the flotation products demonstrated severe masking of fine particles on the surface of quartz. The extended-DLVO (Derjaguin-Landau-Verwey-Overbeek) theory was applied to calculate the interaction energy between the mineral particles, and the results showed that the interaction force between magnesite and quartz and between dolomite and quartz was attractive; therefore, fine magnesite and dolomite particles were easily masked on the surface of quartz. The calculation results agree with the experiment results and explain the mechanism of particles' interaction and the reasons for the differences in single mineral flotation and artificially mixed minerals flotation.