It’s highly challenging to separate feldspar from quartz by flotation owing to their similar crystal structure and physicochemical properties. Using mixed collectors has become a promising method to improve the quartz-feldspar separation. In this study, mixed dodecyl amine (DDA) and sodium petroleum sulfonate (SPS) surfactants were used in the flotation separation of feldspar and quartz, and the adsorption mechanism of mixed collectors and depression mechanisms of two depressants were investigated through zeta potential, contact angle and Fourier transform infrared (FT-IR) spectra. When the pH reached 4.5, the separation of feldspar from quartz was more obvious. In the presence of DDA/SPS collector, the contact angle of feldspar was increased more obviously leading to enhance hydrophobicity. The infrared spectra revealed the interaction of collectors on feldspar surface involved physical and chemical adsorption, whereas the adsorption of collector on quartz was only physical interactions. The use of sodium hexametaphosphate resulted in a significantly enhanced separation performance. The weaker physical adsorption of mixed collector on quartz can be destroyed by sodium hexametaphosphate. This study is beneficial for understanding the collect mechanisms of mixed cationic-anionic surfactants on quartz and feldspar minerals, and promotes the development of advanced feldspar separation techniques.