As an ageless "nano-element" in trees, plants and other cellulose-containing species, cellulose nanocrystal (CNC) has been widely used as a renewable building block in diverse applications. Traditional modification strategy of CNC is based on the reaction with its surface hydroxyl groups, suffering the change of its surface physiochemical properties. In this study, a regio-selective and local modification strategy was performed on the reducing end of CNC with the grafting of long-chain poly(ethylene oxide) (PEO) to produce the end-grafted nanocrystals (CNC-eg-PEO). Based on thiol-ene click reaction, the terminal allyl-PEO was covalently attached on the modified nanocrystal possessing the reactive thiol groups. With the preservation of surface chemistry, the redispsersion stability of CNC-eg-PEO was promoted, attributed to the dual effect of steric stabilization and electrostatic repulsion. Furthermore, the CNC-eg-PEO exhibited the low cytotoxicity to ATCC cell lines HFF and CAL-27, indicating its promising biomedical application. (c) 2021 Elsevier B.V. All rights reserved.