In this work, selective flotation separation of microfine apatite and chlorite was achieved by using sodium oleate (NaOL) as a collector with a low dosage of acidified sodium silicate (ASS) as a depressant. The optimum ratio of sodium silicate to sulfuric acid for ASS was 5:3, and a good separation effect was also achieved in the mixed ore system. Compared to the deionized water system, the ions of Na+, Ca2+ and Mg2+ in seawater adsorbed on the surfaces of apatite and chlorite, which made the zeta potential of the two minerals shift positively. This presented a challenge to the selection of reagents for mineral separation. The addition of ASS changed the pH value of the pulp from weak alkalinity caused by seawater to weak acidity, which allowed the metal ions adsorbed on the mineral surface to desorb. Meanwhile, ASS can selectively adsorb on the desorbed chlorite surface in the form of Si(OH)4, which hindered the action of NaOL, leading to the depression of chlorite. NaOL adsorbed well on the desorbed surface of apatite and increased the apatite particle size from 27 μm to 229 μm, with a hydrophobic agglomeration effect, thus enhancing the flotation of microfine apatite.