Chitosan is a natural polysaccharide exhibiting excellent biocompatibility, biodegradability and nontoxicity, making Chitosan-based biomaterials ideal drug delivery systems and cell carriers for tissue engineering. The electrospinning technique, with optimized parameters, was used to fabricate chitosan/PVA as-spun mats. Field emission scanning electron microscopy (FESEM) was used to investigate the morphologies of the as-spun mats. We present a novel electrospun nanofiber-based drug delivery. In this system, genistein was loaded on nanofiber mats via three methods namely; passive loading, crosslinking after passive loading, and active loading. The way in which genistein was loaded significantly influenced its in-vitro drug release characteristics. The in-vitro release studies revealed that physical cross-linked nanofibers have a significantly delayed release demonstrating 21% progressive release after 30 min and 69% after 24 h, which is considered a superior drug delivery system compared to those reported before for genistein release. 2016 Elsevier B.V. All rights reserved.