Novel multifunctional poly(ethylene oxide) (PEO) nanofibrous membrane, which contains vesicles constructed by mixed surfactant cetyltrimethylammonium bromide (CTAB)/sodium dodecylbenzenesulfonate (SDBS), has been designed as dual drug-delivery system and fabricated via the electrospinning process. 5-FU and paeonolum, which are hydrophilic and hydrophobic anticancer model drugs, can be dissolved in vesicle solution's bond water and lipid bilayer membranes, respectively. The physicochemical properties of the electrospun nanofibrous membrane were systematically studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FTIR), and X-ray diffraction (XRD). Drug release behaviors of the electrospun nanofibrous membrane fabricated with different molar ratio of CTAB/SDBS vesicle solution were investigated. The result showed that the releasing amount of hydrophilic drug presented an ascending release manner, while the hydrophobic one showed a descending release behavior with increasing of the molar ratio of CTAB/SDBS. Moreover, the release amount of drugs from drug delivery system can be controlled by the molar ratio of CTAB/SDBS in the vesicle solution easily and conveniently. The distinct properties can be utilized to encapsulate environmental demanding and quantificational materials.