Although the special architecture of two-dimensional (2D) nanomaterials endows them with unique properties, their poor colloidal stability remains a main bottleneck to fully exploit their applications in the biomedical field. Herein, this study aims to develop a simple and effective approach to in situ incorporate 2D graphene oxide (GO) nanoplatelets into a thermosensitive matrix to acquire hybrid nanogels with good stability and photothermal effect. In order to improve its stability, GO firstly underwent silanization to its surface with double bonds, followed by intercalation with N-isopropylacrylamide (NIPAM) in the presence of a disulfide-containing crosslinker via an emulsion method. Radical polymerization was then initiated to accelerate direct GO exfoliation in PNIPAM nanogels by forming covalent bonds between them. The well-dispersed GO nanopletlets in the nanogels not only displayed an enhanced photothermal effect, but also improved the encapsulation efficiency of an anticancer drug. The hybrid nanogels accelerate drug release under conditions mimicking the acidic/reducible solid tumor and intracellular microenvironments, most importantly, it can be further enhanced via remote photothermal treatment. The multifunctional nanogels potentiate their synergistic anticancer bioactivity as an ideal nanoplatform for cancer treatment.