Surface coordination chemistry is important in areas such as adsorption, separation, and catalysts. In this work, surface coordination interactions of benzohydroxamic acid (BHA) with the lead ion [Pb(II)] adsorbed on the cassiterite surface have been investigated by first-principles calculations due to its great significance in froth flotation. Cluster calculations show that BHA possesses the weakest chelation with Pb(II) due to the electron withdrawal ability of the benzyl ring in comparison with other hydroxamic acids. Pb(II) thermodynamically prefers to react with the cassiterite surface rather than BHA. On the other hand, the partial density of states and the atomic overlap populations have consistently verified that the adsorption of BHA results in a better symmetry in electron densities than the hydrated Pb(II). The electron density maps and the electronic localization functions have further visualized the rearrangement of the 6s2 lone pair around the lead atom. It can be concluded that the surface coordination mechanisms of Pb(II) on oxide minerals can be attributed to the coordination ability of BHA and the unique electronic structure of Pb(II), which accounts for the reported better flotation performance of the pre-assemble strategy than the pre-activating approach. This work sheds some new light on the unique coordination activation mechanism of metal ions on oxide mineral surfaces. It should be instructive to design and screen new environment-friendly flotation reagents and flotation flowsheets.