Hypothesis: How to encapsulate poly(N-isopropylacrylamide) (PNIPAM) mesoglobule cores by silica shells greatly affects the resultant nanoparticle structures. Incorporation of acrylamide (AM) unit into PNIPAM in combination with 3-glycidyloxypropyltrimethoxysilane (GLYMO, as a coupling agent) effectively induces nucleation and growth of silica on PNIPAM core surfaces, where the –NH2 of acrylamide reacts with the epoxide of GLYMO while GLYMO further participates in subsequent sol-gel reaction of tetraethyl orthosilicate (TEOS), thereby leading to desirable particle morphology. Experiments: PNIPAM-based core–silica shell nanoparticles were prepared by sol-gel reaction of TEOS and GLYMO in the presence of polymeric core particles. The major parameters investigated in a systematic fashion include acrylamide concentration and weight ratio of polymer:GLYMO:TEOS. GPC, DLS, DSC, FE-SEM, TEM, FTIR and TGA were then used to characterize polymeric cores and hybrid nanoparticles. Findings: The particle morphology was governed primarily by the acrylamide content and the weight ratio of PNIPAM/AM:GLYMO:TEOS, and desirable hybrid nanoparticles with narrow particle size distribution were achieved. The LCST of PNIPAM-based mesoglobules increases with increasing acrylamide content. Encapsulation of PNIPAM-based mesoglobules with silica also reduces their thermosensitivity. This is the first report of developing a novel approach to prepare PNIPAM-based mesoglobule core–silica shell nanoparticles with controllable particle morphologies.