Resveratrol has been reported as a potential antitumor agent for several years. The possible application was greatly hampered by its poor solubility. The current study reported the construction of electrospun Resveratrol loaded nanofibers with methoxypolyethylene glycol-poly(caprolactone) (mPEG-PCL) block copolymers as drug carriers. Characterization studies showed the successful encapsulation of Rsv in the nanofibers with an in vitro sustained release pattern. In vitro XTT assay suggested the superior cytotoxicity of Rsv-NFs with more apoptosis induction on cancer cells. Cells that exposed to Rsv-NFs showed less clonogenic ability when compared to the equivalent dose of free Rsv. In addition, the migration and invasion ability of cells were also significantly lower when treated with Rsv-NFs. In the in vivo study, local implantation of Rsv-NFs greatly increased the growth inhibitory effect compared to free Rsv. Therefore, results from the current study demonstrated a promising way to improve the antitumor effect of Rsv by nanofiber delivery.