Interaction mechanism of fine wolframite with octyl hydroxamic acid (OHA) during flotation process was investigated. Flotation and adsorption tests indicated that wolframite showed better floatability as a consequence of OHA adsorption at pH 7.0–10.0. Zeta-potential measurements revealed that OHA adsorbed specifically on wolframite surface. The results of solubility behavior of wolframite indicated that the anion-exchange reaction occurred between OHA− in solution and WO42- in the crystal lattice. OHA− might interact with Mn2+/Fe2+ cations of wolframite surface to form ferrous/manganous hydroxamate precipitations, with a release of WO42- ions. The XPS analysis confirmed that the mechanism of OHA adsorption onto wolframite surface associating coadsorption/surface reaction process was presented in flotation conditions. OHA could bond with ferrous/manganous species on wolframite surface, accompanying molecule OHA physical adsorption onto the chemisorbed layer of ferrous/manganous hydroxamate precipitations. This interaction process appeared to be strong enough to ensure adequate adsorption ability of OHA on wolframite surface and led to good hydrophobicity of wolframite.