The collagen-hyaluronic acid oligosaccharides (collagen-HA) complex was obtained by covalent attachment using EDC/NHS. The cross-linked product collagen-HA had been confirmed by Fourier transform infrared spectra (FTIR) and the sulfuric acid-carbazole colorimetry, and factors that affect the cross-linking process were investigated. Electrospinning of collagen-HA complex in hexafluoroisopropanol was investigated for the biomimetic nanostructure and biocompatible vascular tissue-engineered inner-layer scaffold. The morphology of the electrospun collagen-HA nanofibers with a series of concentrations was observed by scanning electron microscopy. The thermal behavior and chemical properties of the fabricated scaffolds were characterized using dynamic scanning calorimetry and FTIR after being stabilized by glutaraldehyde vapor. The cell attachment, morphology and proliferation of porcine iliac artery endothelial cells (PIECs) on the electrospun scaffolds were also evaluated. The results indicate that the biomimetic matrix collagen-HA electrospun nanofibrous scaffold could promote PIECs proliferation and may be a better candidate with endothelial potential for the vascular tissue-engineered inner-layer scaffold.