Nanoparticles (NPs) functionalized with polymers have a broad range of applications; however, a key challenge is to achieve high-yield and time-efficient isolation of the polymer-capped NPs from free polymers. Here, we introduce a highly effective thermodynamically driven approach to isolate polymer-grafted NPs. By controllably reducing the solvent quality for the polymer tethers, cellulose nanocrystals end-grafted with poly(N-isopropyl acrylamide) (pNIPAm) were isolated from free pNIPAm. More specifically, under poor solvency conditions, polymer-tethered NPs aggregated and precipitated, while the free polymer remained in the supernatant. The method was validated for the NPs end-grafted with pNIPAm with different molecular weights. The approach was theoretically rationalized using a scaling approach. Based on the NP isolation time and separation efficiency, the solvent-mediated method favorably compared with conventional dialysis and membrane filtration separation techniques and thus can be used for a variety of polymer-functionalized NPs.