In contrast to systemic chemotherapy, the local administration of chemotherapeutics potentially optimizes their accumulation in the tumor tissues and alleviates the associated systemic toxicity. However, the lack of control over the release of encapsulated drugs and their degradation represents a major challenge for local drug delivery systems. In this study, we developed a series of epirubicin (EPI)-loaded poly(ε-caprolactone)/poly(lactide-co-glycolide) (PCL/PLGA) nanofiber capsules with adjustable rates of drug release and degradation for local malignancy chemotherapy. The core-sheath PCL/PLGA nanofiber capsules containing 15.0 or 25.0 wt% of PCL in the sheath and 0, 5.0, or 10.0 wt% of EPI in the core were produced by emulsion electrospinning technology. The EPI release and degradation of the nanofiber capsules could be accelerated by decreasing the PCL content in the sheath. More importantly, the EPI-loaded PCL/PLGA nanofiber capsules effectively inhibited the growth of tumor cells in vitro and in vivo. Moreover, none of the laden nanofiber capsules caused apparent systemic toxicity. Hence, the cytostatic-loaded electrospun polyester nanofiber capsules displayed controlled drug release and degradation, along with satisfactory antitumor properties, indicating their great potential in local malignancy chemotherapy.