It is known that the flotation separation of scheelite and calcite is quite difficult due to their similar surface properites. To slove the problem, ethylenediaminetetra (methylene phosphonic acid) sodium (EDTMPS), an environmentally friendly reagent, was employed as an efficient depressant for flotation separation of calcite for the first time. In flotation experiments, it demonstrates that EDTMPS could strongly inhibit the flotation of calcite but barely affect the flotaiton behavior of scheelite, showing excellent dpress ability and selectivity. Based on a series of measurements including contact angle analysis, zeta potential, and XPS analysis, it was found that large amout of EDTMPS could be absorbed on the surface of calcite through strong chemical chelation reaction and thus inhibiting the further adsorption of NaOL. On the contrary, little EDTMPS was absorbed on that of scheelite owing to the negatively charged tungstate ions on the surface in relative terms. All in all, these results exhibit EDTMPS has excellent selective inhibition ability on calcite, which can be potentially applied in actual scheelite and calcite flotation separation process.