Lizardite slime coating is one of significant factors in the deterioration of the floatability of sulphide minerals. In this study, a nanoparticle cationic polystyrene-co-poly(n-butylacrylate)(PS-PBNH) collector was introduced to eliminate the negative impact of lizardite slimes in pyrite flotation. Microflotation results demonstrated that lizardite slims did not affect the recovery of pyrite in the presence of PS-PBNH. Good flotation separation of pyrite from lizardite was achieved when the nanoparticle PS-PBNH collector was used. The results from adsorption study indicated that PS-PBNH exhibited a significant adsorption on the pyrite surface in the presence of lizardite slimes. Sedimentation tests showed that hetero-aggregation occurred between lizardite slimes and pyrite, whereas the introduction of PS-PBNH collector resulted in a heterogeneous dispersion between them. Zeta potential measurements suggested that PS-PBNH collector interacted with pyrite surface, and the PS-PBNH adsorption changed the surface charge of pyrite from negative to be positive. As a result, the interaction of pyrite with lizardite shifted from electrostatic attraction to electrostatic repulsion, as supported by the DLVO calculations. These results indicated PS-PBNH can be used as a potential collector for pyrite flotation in pyrite/lizardite slimes system without the need for a depressant.