To overcome the difficulty of separating bastnaesite from fluorite through the flotation technique, the present study examined the suitability of sodium alginate (SA) as a depressant in the flotation process. The effect of SA on the flotation separation of bastnaesite and fluorite was evaluated using micro-flotation tests, zeta potential measurements, adsorption density measurements, Fourier infrared spectroscopy, and X-ray photoelectron spectroscopy. The micro-flotation results showed that SA exerted a strongly detrimental effect on fluorite flotation, while slightly affecting bastnaesite flotation. The surface chemistry results revealed that the -COO- and HO- functional groups in SA coordinated with Ca2+ on the fluorite surface, which induced hydrophilicity and hindered adsorption in the subsequent octylhydroxamic acid as a collector. However, the interaction of SA with the bastnaesite surface was marginal and did not affect the anchoring of the collector on the surface of bastnaesite. Based on these results, the present study proposes a possible model for the interaction of SA on the surfaces of the two minerals, laying a foundation for the flotation separation of bastnaesite from fluorite with SA as an environmentally benign depressant.