Bastnasite is an important mineral resource in the production of rare earth materials and is usually beneficiated by flotation. The flotation of bastnasite is problematic due to the competitive adsorption of hydroxamate collector on bastnasite and its associated calcium-bearing gangue minerals such as fluorite. One strategy to solve this problem is to use effective depressants to depress the gangue minerals. However, the current depressants all have some drawbacks. In this study, the effect of ethylenediamine tetraacetic acid (EDTA) as a depressant was tested in the flotation of single mineral of bastnasite and fluorite and their mixture. The mechanism underpinning the role of EDTA was investigated through theoretical thermodynamic calculation, zeta potential and Xray photoelectron spectroscopy (XPS) measurements. The results show that fluorite was significantly depressed, while the flotation of bastnasite was almost unaffected when EDTA was present. The separation index between bastnasite and fluorite increased from 1.18 to 12.66 with the increase of EDTA concentration from 0 to 7.79 kg/t. It was found that EDTA could dissolve the chemically adsorbed octyl hydroxamic acid (OHA) on fluorite through the formation of soluble Ca-EDTA complexes, whereas the chemically adsorbed OHA on bastnasite was more stable and could not be transformed into Ce-EDTA spontaneously. Therefore, the flotation of fluorite was selectively depressed by EDTA. The results show that EDTA was a promising depressant for fluorite gangue mineral in bastnasite flotation.