• Artemisia sphaerocephala Krasch. gum (ASKG) was used as depressant first. • The ASKG has an ability to selectively depress the flotation of calcite. • Flotation separation of fluorite from calcite could be realized with ASKG. • The chemisorption strength of ASKG on calcite is stronger than that of fluorite. The effect of Artemisia sphaerocephala Krasch. gum (ASKG) on the flotation separation of fluorite and calcite with sodium oleate (NaOl) as collector was studied for the first time. Results of micro-flotation and artificial mixed mineral experiments proved that ASKG had a strong depression effect on calcite, but the flotation of fluorite was barely effected by ASKG within the pH range studied. Zeta potential analysis results confirmed an evident adsorption difference of ASKG, and the adsorption strength of ASKG on calcite was much stronger than that of fluorite. The results of Fourier-transform infrared spectroscopy analysis suggested that ASKG hardly affected the chemical interaction between NaOl and fluorite, but the pre-adsorption of ASKG on calcite surface could further prevent the adsorption of NaOl. Meanwhile, X-ray photoelectron spectroscopy analysis results indicated that ASKG could be adsorbed on calcite surface to improve the hydrophilicity by the strong complexation of hydroxyl (–OH) with Ca 2+ . Therefore, the flotation separation of fluorite and calcite could be realized due to the remarkable difference of NaOl adsorption by using ASKG as selective depressant.