As a layered silicate mineral, serpentine is easy to slime. Fine serpentine particles can significantly deteriorate the flotation environment and adversely affect flotation indexes. Ascharite and serpentine are the most important non-metallic ores in paigeite ore. They are closely associated with each other and have fine particle size, so they need to be sorted under fine particle size. However, a large quantity of fine serpentine particles not only reduces the recovery of ascharite but also flows into the concentrate with ascharite, leading to the low quality of the concentrate. Effective inhibition of serpentine is the key to solving the problem of as charite flotation from serpentine. As an anion inhibitor, the effect of calcium lignosulfonate (CLS) on the serpentine surface has rarely been studied, and the inhibitory mechanism is unclear. Flotation test, Zeta potential analysis, XRD, and XPS discussed the inhibition mechanism of CLS on serpentine. Flotation test, Zeta potential analysis, XRD, and XPS discussed the inhibition mechanism of CLS on serpentine. The experimental results show that serpentine can significantly reduce the recovery rate of ascharite flotation when pH>8. As the pH value increased to 10, the recovery of ascharite decreased to 42.8%, and the serpentine recovery was 17.6% in concentrate simultaneously. However, the serpentine recovery was reduced to less than 5% and the ascharite recovery was up to about 66% when the 20~40 mg·L-1 CLS was used in flotation. The mechanism analysis shows that the adsorption of CLS on the serpentine surface can reduce the Zeta potential of serpentine, which is attributed to influences of chemical adsorption and hydrogen bonding. The former is achieved by forming a bond with the Mg atom on the serpentine surface, and the latter is the result of the interaction between the phenolic hydroxyl group of CLS and the hydroxyl group in serpentine.