To improve the flotation separation efficiency of smithsonite from quartz using N,N'-dilauroyl ethylenediamine dipropionate (DNET) as a collector, sodium carbonate was used as a regulator. Single-mineral flotation results indicated that more than 97.36% of smithsonite was floated when DNET was used as a collector at a concentration of 200 mg/L. However, artificially mixed minerals were poorly separated during the activation of quartz with Zn(II) due to smithsonite dissolution. Sodium carbonate could inhibit the dissolution of smithsonite and thus improve the flotation separation of smithsonite and quartz. The results of artificially mixed mineral separation showed that a concentrate with 89.7% Zn recovery and 36.6% Zn grade could be obtained when the DNET concentration was 50 mg/L at a slurry pH of 10.45. To clarify the action of sodium carbonate during the separation process, zeta potential measurements, Fourier transform infrared (FTIR) spectroscopic analysis, and zinc ion concentration measurements were carried out. In addition, the results indicated that sodium carbonate could inhibit the solubility of smithsonite, and thus, the activation of quartz was prevented during the interaction of CO32-with dissolved Zn(II), thereby improving the separation results.