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A new type of cellulose derivative was synthesized by means of conjugating cysteamine to hydroxypropyl cellulose (HPC) and the degree of thiol groups could be controlled by the feed ratio of the reactants. The thiolated HPC (HPC–SH) maintains the thermosensitivity of HPC and the thiol groups on the HPC chain can be oxidized to disulfide bonds. Cytotoxity tests performed on MG-63 cells proved that HPC–SH is not harmful to the cells. Nanogels can be fabricated by the self-association of HPC–HS in the solution at 45 °C and then oxidation of thiol groups to disulfide bonds occurs to stabilize the associated structure. The crosslinking degree of the nanogels could be controlled by the substituion degree of thiol groups (–SH) in the thiolated HPC. The hydrodynamic radius of the nanogels can be tuned by adjusting the degree of crosslinking and the concentration of the initial thiolated HPC solution in the self-association process. The hydrodynamic radius of the nanogels can be changed with the temperature and the dissociation process can happen by adding the reducing agent dithiothreitol (DTT). The dual-stimuli sensitive nanogels may have potential applications in controlled drug release, transfer switch device and sensors.