The performance of the mixed dodecylamine chloride (DDA)/octanol (OCT) surfactants on muscovite flotation was investigated using flotation tests, and their adsorption mechanisms on muscovite and air/water interface were clarified using contact angle measurement, surface tension and molecular dynamics (MD) simulations. The flotation results indicate that the recovery of muscovite rapidly decreases when the pH increases in the presence of only DDA, whereas the recovery of muscovite is high (> 77%) over a wide range of pH in the presence of the mixed DDA/OCT surfactants with a ratio of 2/1. Contact angle measurements further confirm that the mixture displays a stronger collecting power than DDA and is a superior collector for the muscovite flotation. The surface tensions of DDA, OCT and their mixture indicate that the mixture is more efficient than DDA at decreasing the air–water interfacial tension and exhibits much better surface activities. MD simulations show that the mixture interacts with the muscovite mainly through electrostatic attraction and hydrogen-bonding. DDA ion is dominant in the interaction between the mixture and muscovite. OCT molecules are co-adsorbed onto the muscovite through the hydrogen-bond interaction and hydrophobic association with DDA ions. Compared with DDA, a well-compacted monolayer is formed on the muscovite surface in the presence of mixed surfactants, indicating a much stronger hydrophobic character of muscovite.