We report an efficient approach for the fabrication of hydrophobic drug-loaded human serum albumin nanofibers for the first time. The successful formation of nanofibers was found closely related to the glutathione (GSH) concentration, solution temperature, and heating time. As-fabricated nanofibers were characterized by electron microscopy, Fourier transform infrared spectroscopy (FTIR) and X-ray powder diffraction (XRD). The electron micrographs show that nanofibers have cylindrical morphology and diameters of 70-120 nm and lengths of up to few micrometers with a smooth surface. GSH was found to contribute to the quicker unfolding of the HSA under high temperature (80-85(circle)C) which resulted in the strong interaction with paclitaxel, leading to a morphological transformation from nanoparticles to nano fibers. In addition, the possible mechanisms of nanofiber formation have been discussed. (C) 2016 Published by Elsevier B.V.