In this study, pure silica nanofibers (SNFs) were fabricated by the electrospinning technique. Subsequently, the as-prepared SNFs were modified with (3-aminopropyl) trimethoxysilane (APTS) for applications in neural tissue engineering. The structure and properties of the as-prepared SNFs and the modified SNFs (SNF-APxM, x = 1-3) were evaluated with FTIR, TGA, nitrogen adsorption/desorption isotherms, and SEM. It was found that the surface hydrophilicity of SNF-APxM was lowered upon increasing the amino alkyl group content. The SEM and confocal images revealed that neural stem cells (NSCs) cultured on the electrospun SNFs and SNF-APxM substrates were elongated along the fibers in comparison to poly-D-lysine-coated (PDL-coated) substrate. In addition, a higher degree of proliferation and more responsive cells were observed for the NSCs cultured on the SNF-AP3M substrate than those on the SNFs and the PDL-coated substrates. The results indicated that the APTS-modified silica nanofibers can be potential substrates for regulating growth and differentiation of NSCs in culture.