The selective isolation of specific proteins from complex protein mixtures by nanoparticles is reported. Glutathionemodified superparamagnetic nanoparticles were used to purify specific proteins fused with glutathione S-transferase via enzyme-substrate interactions. They demonstrated greatly improved selectivity and efficiency over micron sized capturing beads. The ultra-specific enrichment of target proteins was confirmed by both SDS-PAGE and LC/MS/MS experiments.