Covalently functionalized graphene sheets are prepared by grafting a well-defined thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) via click chemistry. The PNIPAM-grafted graphene sheets (PNIPAM-GS) consist of about 50% polymer, which endows the sheets with a good solubility and stability in physiological solutions. The PNIPAM-GS exhibits a hydrophilic to hydrophobic phase transition at 33 °C, which is relatively lower than that of a PNIPAM homopolymer because of the interaction between graphene sheets and grafted PNIPAM. Moreover, through π–π stacking and hydrophobic interaction between PNIPAM-GS and an aromatic drug, the PNIPAM-GS is able to load a water-insoluble anticancer drug, camptothecin (CPT), with a superior loading capacity of 15.6 wt-% (0.185 g CPT per g PNIPAM-GS). The in vitro drug release behavior of the PNIPAM-GS-CPT complex is examined both in water and PBS at 37 °C. More importantly, the PNIPAM-GS does not exhibit a practical toxicity and the PNIPAM-GS-CPT complex shows a high potency of killing cancer cells in vitro. The PNIPAM-GS is demonstrated to be an effective vehicle for anticancer drug delivery.