Superparamagnetic iron oxide (SPIO) nanoparticles are widely used in magnetic resonance imaging (MRI) as versatile ultra-sensitive nanoprobes for cellular and molecular imaging of cancer. In this study, we report a one-step procedure for the surface functionalization of SPIO nanoparticles with a lung cancer-targeting peptide. The hydrophobic surfactants on the as-synthesized SPIO are displaced by the peptide containing a poly(ethylene glycol)-tethered cysteine residue through ligand exchange. The resulting SPIO particles are biocompatible and demonstrate high T(2) relaxivity. The nanoprobes are specific in targeting α(v)β(6)-expressing lung cancer cells as demonstrated by MR imaging and Prussian blue staining. This facile surface chemistry and the functional design of the proposed SPIO system may provide a powerful nanoplatform for the molecular diagnosis of lung cancer.