Impact statement The behaviors for the controlled release of drugs loaded in the thermosensitive electrospun nanofibers could be affected by various factors including the properties of loaded drug, morphologies of nanofibrous, and lower critical solution temperatures of thermosensitive hydrogels. However, few systematical investigations have been performed in this area. In this article, we designed and fabricated porous and coaxial thermosensitive poly(N-isopropylacrylamide) electrospun nanofibers with different drug loading to study the comprehensive effect. This study suggested when adopting thermosensitive electrospun hydrogel nanofibers as the controllable drug release carrier, the hydrophilicity of loaded compounds and the morphologies of nanofibers are necessary to be optimized. Electrospun nanofibers is a promising and versatile avenue for building controlled drug release system because of the facile fabrication and the broad range of polymer materials. This research systematically studied the morphological effect of thermosensitive electrospun nanofibers, including porous and coaxial structures, on controllable drug release. Three types of drugs, nicotinamide, paracetamol, and ibuprofen, with different hydrophilicity were applied in this study. The data of drug release were all fitted to the first-order kinetic model regardless of the drug properties, and the release rates paralleled with their hydrophilicity. Sol-gel phase transition of the thermosensitive poly(N-isopropylacrylamide) (PNIPAAm) hydrogel led to slower drug release at 37 degrees C compared with those at 25 degrees C. Regarding morphology, coaxial nanofibers could provide higher loading efficiency and slower drug release rather than porous nanofibers. Our research highlighted the overall effects of compound property, temperature, and the morphological structures of thermosensitive electrospun nanofibers on the controlled drug release. Our results concluded that hydrophobic drug encapsulated in the core-shell PNIPAAm nanofibers could perform excellent sustained release and also controllable release under temperature stumuli.