To engineer tissue restoration, it is necessary to provide a bioactive, mechanically robust scaffold. Electrospun poly( epsilon-caprolactone) (PCL) nanofiber is a promising biomaterial candidate with excellent mechanical properties, but PCL scaffolds are inert and lack natural cell recognition sites. To overcome this problem we investigated the incorporation of Antheraea pernyi silk fibroin (ASF) containing inherent RGD tripeptides with PCL in electrospinning process. The mixing ratios showed remarkable impact on the properties of hybrid nanofibers. Increasing PCL content significantly enhanced the mechanical properties of nanofibers. In particular, the mechanical properties were remarkably enhanced when PCL content increased from 50 wt% to 70 wt%. Moreover, the biological assays based on endothelial cells showed promoted cell viability when ASF content reached to 30 wt%. The data demonstrated that the nanofiber containing 70% of PCL and 30% of ASF achieved the most balanced performances for integrating the mechanical properties of PCL and the bioactivity of ASF. Furthermore, biomimetic alignment of 70PCL/30ASF nanofibers was achieved, which could support PC12 neuron-like cell growth and guide neurite outgrowth, providing a potentially useful option for the engineering of oriented tissues. The results show that the PCL/ASF hybrid nanofibers can be considered as a promising candidate for tissue engineering scaffolds. POLYM. ENG. SCI., 57: 206-213, 2017. (C) 2016 Society of Plastics Engineers