Smart polymers with extraordinary characteristics are studied in drug-delivery applications. In the current study, temperature-responsive hybrid core-shell nanoparticles were synthesized by precipitation polymerization of N-isopropylacrylamide and vinyl-modified silica nanoparticles. These temperature-responsive hybrid core-shells were prepared with different cross-linking densities by using 2, 4, and 8 mol % of N,N-methylene bisacrylamide (MBA). Hydrolysis of the silica cores of the hybrid core-shells resulted in hollow poly(N-isopropylacrylamide) (PNIPAM) nanogels. Functionalization of silica nanoparticles with vinyl-containing silane modifier of 3-(trimethoxysilyl) propyl methacrylate (MPS) in two different contents was proven by Fourier transform infrared spectroscopy. Preparation of the hybrid PNIPAM nanogels and etching of the silica cores were studied using thermogravimetric analysis and also electron microscopy imaging. Sensitivity of the PNIPAM nanogel samples to temperature was studied using ultraviolet-visible (UV-vis) spectroscopy. In addition, dynamic light scattering was used for investigation of the squeezing and expansion of the hybrid and hollow samples against variation of temperature. The UV-vis spectroscopy results display higher absorption intensities in higher contents of MPS modifier and MBA cross-linker. The swelling content of the nanogels with hollow cavities was higher than that of the hybrid samples. The hybrid nanogels with 2 and 8 wt % silica content and different cross-linking densities and also their hollow nanoparticles were used for loading and release of doxorubicin (DOX). The release characteristics of the DOX-loaded nanogels were studied at different temperatures using UV-vis spectroscopy. The DOX release was higher at temperatures lower than the gel collapse temperature of the PNIPAM network. Although the nanogels with hollow cavities displayed higher loading capacities, the release percentage was higher for the hybrid PNIPAM nanogels, which was confirmed by the experimental release profiles and mathematical models. The most appropriate fitting of the DOX release data from the PNIPAM nanogel samples was observed for the Korsmeyer-Peppas model. Cytotoxicity studies on HeLa cell line showed that drug-loaded hollow samples showed higher toxicity due to loading of a higher amount of DOX.