Abstract: A lepidolite ore containing 1.09% Li₂O was taken as the research object. Three anionic collectors (sodium oleate (NaOl), sodium dodecyl sulfonate (SDS) and sodium naphthenate (NA)) were combined with cationic collector (dodecylamine (DDA)), respectively, and the synergistic mechanism of mixed anionic/cationic collectors on lepidolite flotation was studied from the perspective of the gas-liquid interface by means of flotation experiment, surface tension, physicochemical property of foam and activity coefficient. The flotation results showed that the flotation performance of these three mixed anionic/cationic collectors was better than that of a single collector. When the molar ratio of DDA to SDS was 1∶1, the flotation performance was the best, and the grade and recovery of Li₂O of the concentrate were 2.24% and 61.88% respectively. Meanwhile, the stability of flotation foam was the lowest, which was conducive to lepidolite flotation. The height, half-life and water content of the flotation foam were 33 mm, 86 s and 48.72% respectively. The results of surface tension and activity coefficient showed that the anionic collectors were inserted into the gaps between DDA cations and intertwined each other by electrostatic force and hydrophobic association between carbon chains in the mixture systems. Due to the strong electronegativity, the sulfonic groups had a stronger ability to neutralize the positive charges carried by the amine groups. Compared with DDA/NaOl and DDA/NA, the saturation adsorption value of DDA/SDS at the gas-liquid interface increased, and the average minimum area per molecule decreased, showing higher surface activity and better collection ability and selectivity for lepidolite.