In the last years, chitosan (CS) nanofibers as one of the biodegradable biomaterials in nature for tissue engineering and related fields, including wound healing and cell-material interaction, have been widely used. For this purpose, we prepared the reinforced CS/nanocrystals cellulose-graft-poly(N-vinylcaprolactam) (CS/NCC-g-PVCL) nanofibers via the electrospinning technique. Fabricated nanofibers were characterized and studied for their structural, morphological, thermal stability, as well as mechanical and hydrophilic properties. Uniform nanofibers were achieved, and NCC-g-PVCL contents were partially embedded into CS nanofibers, as revealed in SEM analyses. Incorporation of NCC-g-PVCL contents (0.5, 2.5, and 5 wt%) enhanced the average fiber diameter of the obtained nanofibers from 100 nm (neat CS) to similar to 350 nm [CS/NCC-g-PVCL (5 wt%)] and improved the nanofibers thermal stability. Additionally, among the CS/NCC-g-PVCL nanocomposite fibers, those loaded with 5 wt% NCC-g-PVCL had the best mechanical properties. The water contact angle of nanocomposite nanofibers increased with elevation of the weight content of NCC-g-PVCL. Cell culture results showed that the prepared nanofibers had better cytocompatibility and proliferation than neat CS nanofibers. The results proposed that the developed CS/NCC-g-PVCL nanocomposite nanofibers were promising as new biomaterials to be applied in the area of skin tissue engineering.