Common reverse flotation is difficult to separate efficiently picromerite with a high halite content. This work employed direct flotation to separate picromerite and halite, using sodium dodecyl benzene sulfonate (SDBS) as a novel picromerite collector. The flotation performances were evaluated by single and real ore flotation tests, with results indicating that K+ recovery was 95.89%, while Na+ content was less than 2% in the concentrate at an SDBS dosage of 200 g/t, which suggested SDBS was an effective picromerite collector with excellent separation performance. The interaction mechanism was investigated by adsorption experiment, Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscope and Energy Dispersive Spectrometer (SEM-EDS), and X-ray Photoelectron Spectroscopy (XPS) analysis. The adsorption experiments demonstrated that picromerite had a stronger affinity to SDBS than halite, confirming that SDBS exhibited good selectivity in the flotation of picromerite and halite. FTIR and SEM-EDS analysis revealed that SDBS adsorbed on the picromerite surface. XPS results further unveiled that SDBS chemisorbed on the picromerite surface through the strong complexation between sulfonic acid groups and Mg atoms on the picromerite surface, forming O-Mg bonds. This study provides a new perspective on the efficient separation of picromerite and halite, facilitating a high production efficiency of picromerite.