Using microflotation experiments, this study investigated the effect of Pb2+ ions on flotation performance of cassiterite (SnO2) by using benzohydroxamic acid (BHA) as collector. Flotation results showed that floatability of cassiterite significantly improved after addition of Pb2+ ion to the process. Adsorption behaviour and mechanism of BHA on the inactivated and Pb-activated cassiterite surface were further explored by adsorption experiments, zeta potential measurements, X-ray photoelectron spectroscopy analysis and first-principle density functional theory calculations. Experimental and computational results consistently suggested that the adsorbed Pb atoms can coordinate with two O atoms of the two hydroxyl groups on the cassiterite surface. BHA molecules can form two coordination bonds with one Pb ion adsorbed on the cassiterite surface, resulting in a five-membered chelating ring. The proposed adsorption mechanism can be extended to the vast majority of interface assembly systems.