Abstract A considerable amount of very fine particles can be found, e.g., stored in tailing ponds, and they can include valuable or hazardous minerals that have the potential to be recovered. Selective flocculation, i.e., the formation of larger aggregates from specific minerals, offers a promising approach to improve the recovery of ultrafine particles. This study focuses on the use of a new bio-based flocculation agent made of silylated cellulose nanofibers containing a thiol-functional moiety (SiCNF). Flocculation was performed in separated systems of ultrafine mineral dispersions of pyrite, chalcopyrite, and quartz in aqueous alkaline medium. The flocculation performance of SiCNF was addressed in terms of the turbidity reduction of mineral dispersions and the floc size, and the results were compared with the performance of a commercial anionic polyacrylamide. SiCNF exhibited a turbidity removal efficiency of approximately 90%–99% at a concentration of 4000–8000 ppm with chalcopyrite and pyrite, whereas the turbidity removal of quartz suspension was significantly lower (a maximum of approximately 30%). The sulfide particles formed flocs with a size of several hundreds of micrometers. The quartz in turn did not form any visible flocs, and the dispersion still had a milky appearance after dosing 12,000 ppm of the flocculant. These results open a promising path for the investigation of SiCNF as a selective flocculation agent for sulfide minerals.