Abstract: China's demand for boron resources is robust, yet the supply remains inadequate. Effective recovery of ascharite from the by−products of ludwigite magnetic separation has emerged as a pivotal strategy for improving resource utilization. However, the separation of ascharite from serpentine, a magnesium−bearing gangue mineral, is a significant challenge in this field. The present study is based on the surface characteristics of minerals and the molecular properties of flotation reagents. By optimizing design and utilization mechanism of the reagents, the efficient enrichment and recovery of ascharite in tailings was successfully achieved. Theoretical calculations of mineral crystal planes indicate that the Mg active sites on the surface of ascharite exhibit higher electronic activity, while the surface of serpentine, which exhibits poor surface floatability, is predominantly rich in silicon and oxygen sites. The design of three types of collectors (OA−1, OA−2, and OA−3) was informed by the prevalent use of oleic acid. This design was achieved through a series of chemical reactions, namely sulfuric acid oxidation, carboxyl carbon atom oxidation, and hydrogen peroxide oxidation. The OA−n collector was produced by mixing in a ratio of 8∶1∶1 with the three collectors. The experimental results demonstrate that the optimized collector OA−n exhibits superior properties in terms of solubility, dispersion, and selectivity when compared to the traditional oleic acid. A comprehensive investigation was carried out to determine the effect of various parameters on the flotation effect, encompassing the collector dosage, inhibitor type and dosage, pulp pH, and temperature. Through experimentation, it was determined that the optimal conditions for flotation were as follows: 600 g/t collector dosage, 6000 g/t depressant dosage, pulp pH of 9.00 and temperature of 30 ℃. The synergistic application of OA−n and acidified sodium silicate resulted in an exceptional flotation index of ascharite B₂O₃, with a B₂O₃ grade of 9.98% and a recovery of 61.22%. The analysis show that following the introduction of hydroxyl groups, the optimized OA−n collector enhance solubility and dispersion performance, while concurrently introducing a novel action site that binds to the surface active site of ascharite. The incorporation of acidified sodium silicate is shown to significantly reduce the floatability of serpentine, a phenomenon attributable to the formation of hydrophilic silica colloidal particles on the surface of the latter. This in turn leads to an increase in the separation efficiency between ascharite and serpentine. The present study proposes a reliable scheme for the efficient enrichment and recovery of boron resources in the magnetic separation tailings of ludwigite. This scheme is based on the synergistic effect of a new OA−n collector and acidified sodium silicate. The proposed scheme would significantly reduce the loss of boron resources and solid waste discharge, and provide important technical support for the high value reuse of tailings.