Tungsten and tin are important strategic resources. Scheelite and cassiterite have similar physical and chemical properties and face the challenge of flotation separation. This study proposes soluble starch (SS) as an effective depressant for the flotation separation of scheelite from cassiterite. The depression mechanism of SS was investigated using micro-flotation, zeta potential, total organic carbon, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and time-of-flight secondary ion mass spectroscopy. SS exhibited a good selective depressive effect on cassiterite and was able to efficiently separate scheelite from cassiterite. The results of artificial mixed mineral test showed that the recovery of scheelite and cassiterite were 79.35 % and 9.48 %, respectively and the grade were 70.15 % and 8.11 %, respectively at pH 10. The macromolecular organic depressant SS has abundant hydrophilic groups, such as hydroxyl groups, which cause the material to stably adsorb on Sn active sites on the surface of cassiterite and hinder the adsorption of the collector sodium oleate (NaOL, C17H33CO2Na). The selective adsorption of SS on the surface of cassiterite results in efficient flotation separation of the two minerals.