For biomedical applications, emerging nanostructures requires stringent evaluations for their biocompatibility. Core/shell iron/carbon nanoparticles (Fe@CNPs) are nanomaterials that have potential applications in magnetic resonance imaging (MRI), magnetic hyperthermia and drug delivery. However, their interactions with biological systems are totally unknown. To evaluate their potential cellular perturbations and explore the relationships between their biocompatibility and surface chemistry, we synthesized polymer grafted Fe@CNPs with diverse chemistry modifications on surface and investigated their dynamic cellular responses, cell uptake, oxidative stress and their effects on cell apoptosis and cell cycle. The results show that biocompatibility of Fe@CNPs is both surface chemistry dependent and cell type specific. Except for the carboxyl modified Fe@CNPs, all other Fe@CNPs present low toxicity and can be used for further functionalization and in a wide range of biomedical applications. © 2010 Elsevier Ltd.