In this study, the effects of reagent addition order on the flotation behavior of calcite and fluorite, as well as the influence of acid on the floatation behavior of the calcite, were investigated. Results showed that when the calcite surface had adsorbed the collector, the depression of calcite became increasingly difficult. The presence of acid significantly enhanced the selective depressing effect of depressants on calcite. Actual ore flotation and artificial mixed ore flotation experiments demonstrated that the addition of acid can significantly reduce the calcite content in the concentrate. This phenomenon can be explained by the exposure of the new calcite surface due to the surface dissolution, which facilitated the reaction of calcite with the depressor.