The existence of metal ion should not be ignored in both hydrometallurgy and flotation. In this study, the effects of Ca2+, Mg2+ and Fe3+ on the flotation performance of cassiterite using octanohydroxamic acid (OHA) as the collector were investigated by the micro-flotation tests, X-ray photoelectron spectroscopy (XPS), fourier transform infrared spectroscopy (FTIR), contact angle, zeta (ζ) potential measurements and atomic force microscopy (AFM) imaging. The results of the flotation and contact angle experiments showed that the addition of Ca2+, Mg2+ and Fe3+ significantly decreased both the recovery and contact angle of cassiterite within pH ranged from 6.0 to 12.0 in the presence of OHA collector. ζ–potential measurements, solution chemistry analysis and FTIR measurements indicated that the flotation recovery of the cassiterite declined due to the CaOH+, MgOH+ and Fe(OH)3 sites on the cassiterite surface. XPS results indicated that the chemisorption of OHA on cassiterite surface and its adsorption combined with calcium ions effects finally changed the chemical properties of cassiterite surface. The AFM images also revealed that new species Fe(OH)3 of Fe3+ formed and adsorbed on the cassiterite surface at pH of 9.0. The adsorption of Fe(OH)3 reduced the adsorption of OHA on the cassiterite surface, thus the hydrophobicity of cassiterite was deteriorated.