Electrospun cellulose nanofibers are promising biomaterials but are suffering from the use of unfavorable organic solvents during the electrospinning process. In this manuscript, we used the periodate oxidation-adipic acid dihydrazide crosslinking strategy to fabricate electrospun cellulose nanofibers. Periodate oxidation of cellulose generated water soluble aldehyde cellulose, which thus allowed for the electrospinning in aqueous solution and avoided the use of unfavorable organic solvents. The following crosslinking with adipic acid dihydrazide made the nanofibers water resistant. The results show that the prepared cellulose nanofiber mats show moderate wet mechanical strength around 1 MPa, are able to absorb water equal to 30 times of their own weight, can degrade gradually by hydrolysis, and are cytocompatible. These cellulose nanofibers are expected to find applications in biomedical fields such as wound healing and tissue regeneration. [GRAPHICS] .