Due to the small difference in floatability between dolomite and fluorite, the problems of low grade of fluorite concentrate occur. It is very important to find a depressant that can selectively inhibit the floating of dolomite. As a natural polymer, starch is often used as a gangue depressant because of its low price and easy availability. In this paper, the effects of caustic cassava starch (CS) on the single mineral flotation performance of fluorite and dolomite and the flotation separation of mixed ore were studied. Its selective inhibition mechanism was investigated. The results of flotation tests with single minerals stated that the flotation of dolomite was vastly inhibited, while the fluorite was hardly affected when CS was added in flotation using sodium oleate as the collector. The concentrate grade of artificially mixed ore flotation fluorite reached 90.15%, and the recovery rate was 89.54%. The physical adsorption of CS on the surface of dolomite blocked the adsorption of hydrophobic sodium oleate on the surface of dolomite, thus depressing dolomite. The adsorption energy of dolomite and CS was much larger than that of fluorite and CS. This greatly deteriorated the flotation of dolomite and achieved flotation separation between fluorite and dolomite. The results demonstrate that CS is a promising depressant for dolomite in fluorite flotation.