In the current study, hydroxyethyl cellulose (HEC) based nanofibers were fabricated through electrospinning and then made water insoluble by chemical and photochemical crosslinking. Structural, thermal, and functional performances of electrospun fibers before and after crosslinking were fully assessed by a numerous techniques including microscopy, porosimetry, mechanical analysis, and cell culture study. Both crosslinking procures were found to able to preserve fibrous structure in an aqueous environment for short times, however; chemical process conferred better long-term morphological stability and cell compatibility. These findings suggest that chemically crosslinked HEC mats may perform as a promising electrospun tissue engineering scaffold. (c) 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43832.