Novel temperature-sensitive micelles, possessing a core-shell structure, were successfully fabricated and evaluated as possible systems for targeting anticancer drugs to solid tumors. The amphiphilic block copolymer poly(N-isopropylacrylamide-co-acrylamide)-b-poly(n-butyl methacrylate) was used to achieve a stimuli-responsive on/off release and spatial specificity. The anticancer drug methotrexate, which is poorly water soluble, was used as the model. Fourier transform–infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, gel-permeation chromatography, and critical micelle concentration were used to evaluate the successful synthesis of block copolymers with a lower critical solution temperature ~40°C. Based on transmission electron microscope images, the micelles are spherical particles with narrow size distribution. The thermally triggered release of methotrexate was observed in vitro. Quartz crystal microbalance with dissipation was used to investigate the interactions of the polymeric micelles with bovine serum albumin, to illustrate protein adsorption and cell attachment. Cytotoxicity studies were conducted on Lewis lung carcinoma cells, and the anticancer activity of methotrexate-loaded micelles was significantly enhanced in combination with hyperthermia. The thermo-sensitive characteristics of the micelles make them applicable as smart drug delivery systems, when combined with localized hyperthermia.