The flotation separation of lepidolite from its common gangue minerals (muscovite, quartz, and K-feldspar) remains challenging due to their similar surface properties. This study introduces sodium lignosulfonate (SLS) as a novel selective depressant to enhance the separation efficiency in the presence of the anionic-cationic hybrid collector (OK-84), where dodecylamine serves as the cationic component and vegetable oleic acid as the anionic component. Micro-flotation tests showed that sodium lignosulfonate strongly depressed quartz, K-feldspar, and muscovite while minimally affecting lepidolite floatability. Under optimal conditions (pH = 6, sodium lignosulfonate dosage = 120 mg/L, OK-84 = 80 mg/L), artificial mixed ore flotation achieved a lepidolite concentrate with 2.89 % Li2O grade and 80.12 % recovery. Density functional theory (DFT) calculations revealed that sodium lignosulfonate adsorbed more strongly on gangue minerals (e.g., –290.21 kJ/mol on K-feldspar) than on lepidolite (–150.33 kJ/mol). Fourier transform infrared (FTIR) spectroscopy and zeta potential analyses confirmed chemical adsorption of SLS on gangue surfaces via sulfonate groups, whereas physical adsorption dominated on lepidolite. Contact angle measurements further validated the enhanced hydrophilicity of depressed minerals. Closed-circuit tests on a real lepidolite ore (head grade: 1.53 % Li2O), employing an optimized flowsheet, yielded a final concentrate containing 3.68 % Li2O with 81.07 % recovery, demonstrating the industrial potential of sodium lignosulfonate. This work provides a mechanistic understanding and practical strategy for sustainable lepidolite beneficiation.