So far, much work has been performed to modify graphene by physical or chemical methods, aiming to improve its solubility in solvents for its further application. Herein, we reported a new graphene/polymer nanocomposite, a graphene/poly(N-(2-hydroxypropyl) methacrylamide) (PHPMA) nanocomposite (G-PHPMA), by combining reversible addition–fragmentation chain transfer (RAFT) polymerization and click chemistry under mild conditions via the “grafting-onto” strategy. The as-prepared azido-terminated PHPMA homopolymer via RAFT polymerization was grafted onto yne-containing graphene through click chemistry at room temperature using CuBr/PMDETA as the catalytic system. FT-IR, XRD, Raman, element analysis, TGA, AFM, and TEM measurements were used to confirm the covalent linkage between PHPMA chains and graphene. The resulting G-PHPMA nanocomposite showed excellent dispersibility in organic solvents and aqueous media and it could quickly enter into SMMC-7721 and SH-SY5Y cells.