Nano-sized graphene oxide (NGO) has attracted increasing attention as a drug delivery system (DDS). However, current surface modification and drug loading often rely on covalent conjugation and/or π-π stacking interactions. The current strategy requires either complicated tedious synthesis and/or presence of aromatic moieties on the drug molecules. , whereas non-aromatic species can’t be effectively conjugated or loaded onto NGO via non-covalent manners. Herein, we developed cucurbit[7]uril (CB[7]) functionalized NGO (NGO-CB[7]) that is capable of non-covalent, modular surface functionalization and drug loading via strong host-guest interactions between CB[7] and Ada-tagged molecules, without discrimination against non-aromatic species (Scheme 1). NGO-CB[7] was synthesized via amine-epoxy reaction between NGO and amino-termal CB[7]. For instance, hyaluronated adamantane (HA-ADA) was non-covalently conjugated onto NGO to improve its biocompatibility and physiological stability, as well as to enable targeted delivery to cancer cells overexpressed with CD44 receptors. Meanwhile, doxrubincine (DOX) and oxaliplatin (OX) were loaded onto the surface of NGO through π-π interaction and host-guest complexation, respectively, to realize combined chemotherapy. The sizes and morphology of functionalized NGO were fully characterized by dynamic light scattering (DLS), transmission electron microscope (TEM) and atomic force microscope(AFM). Drug release experiments demonstrated that, under low density of laser irradiation, DOX and OX were released in a controlled manner, as a result of the increased local temperature that weakened the non-covalent interactions. The design of supramolecularly functionalized NGO via host-guest interactions may provide important new insights to functionalization of other carbon nanomaterials and inorganic nanomaterials for the construction of multifunctional nano drug delivery systems.