In this article, the regenerated silk fibroin/2-hydroxypropyl-beta-cyclodextrin/tamoxifen (RSF/2-HP-beta-CD/TAM) composite fibers are successfully prepared via an electrospinning technique. 2-HP-beta-CD/TAM inclusion complex is firstly formed to increase the TAM solubility in the spinning dope. The morphology of the electrospun fibers is investigated, which shows the addition of 2-HP-beta-CD/TAM significantly decreases the fiber diameter. Raman spectra confirm the effective loading of TAM in the resulting electrospun fibers. The drug release behavior of RSF/2-HP-beta-CD/TAM composite fibers indicates that the TAM loaded in such a composite fibers is able to perform a sustainable release. Thus, the TAM-loaded RSF electrospun fibers presented in this report may have a great potential as be a promising local drug delivery system for breast cancer therapy. (C) 2016 Elsevier B.V. All rights reserved.