Hydrofluoric acid production heavily depends on fluorite (CaF2), a mineral frequently occurring alongside other calcium-rich minerals such as calcite (CaCO3). To separate fluorite from calcite and other associated minerals, flotation is the primary method employed. Oleic acid serves as the most commonly used collector in fluorite flotation. However, oleic acid exhibits poor selectivity and limited solubility at low temperatures. A novel fluorite flotation collector, N,9,10-trihydroxyoctadecanamide (THODA), is developed through the modification of the polar functional group of oleic acid, carboxyl, to an N-hydroxy amide group. Additionally, two hydroxy groups are introduced at the double bond position of oleic acid. Flotation experiments demonstrate that employing THODA as a collector can yield a fluorite recovery of approximately 90%, while the recovery rate of calcite ranges between 10% and 20%. THODA exhibits a superior selectivity in the flotation separation of fluorite and calcite compared to oleic acid. Zeta potential experiments reveal that following the treatment with oleic acid, the zeta potential of calcite surface rapidly decreases, whereas after the treatment with THODA, the zeta potential of calcite surface decreases to a lesser extent. This suggests that, under identical dosage conditions, THODA adsorbs less onto calcite surface compared to oleic acid. Consequently, THODA exhibits a weaker ability to collect calcite in comparison to oleic acid, thereby resulting in its enhanced selectivity over oleic acid.