Herein, gelated thermoresponsive large-compound vesicles (LCVs) are reported for the first time. The LCVs are prepared by self-assembly of poly(ethylene oxide)-block-poly[N-isopropylacrylamide-random-3-(trimethoxysilyl)propyl methacrylate] [PEO-b-P(NIPAM-r-TMPM)] in DMF-water mixture. Then, sol-gel reaction of the reactive PTMPM block is performed to stabilize the LCVs. LCVs with higher cross-linking density keep almost the same size under different temperatures while LCVs with lower cross-linking density display obviously thermoresponsive size transition between 22 and 36 °C. The gelated LCVs exhibit enhanced permeability with temperature elevation and their permeabilities at different temperatures all elevate with increasing the cross-linking density.