Abstract: Flotation separation of scheelite and calcite has been a hot research topic. The effect of sodium alginate on the flotation separation of scheelite and calcite in a sodium oleate system was investigated, Density functional theory was used to establish three adsorption models of water−mineral, sodium alginate−mineral, and sodium oleate−mineral, respectively compared the differences in adsorption energy. The results of the study showed thatwhen the dosage of sodium oleate was 50 mg/L, sodium algina was 10 mg/L, and the pH = 9, the recovery of calcite could be controled to 5.20%, while the recovery of scheelite could reach to 83.20%, which showed a significant effect. The molecular simulation results indicated that sodium alginate adsorped on both surface, but the adsorption energy of calcite was stronger than scheelite. After adsorption of sodium alginate, the adsorption energy of sodium oleate on calcite was 43.20 kJ/mol, the adsorption energy of sodium oleate on scheelite was −136.32 kJ/mol. The results demonstrate alginate can selectively inhibit calcite in sodium oleate without affecting scheelite,The AFM image observed also confirmed that a large amount of sodium alginate was adsorbed on the surface of calcite, also provided constructive advice for the separation of scheelite and calcite.