Employing lignocellulosic nanofibers (LCNF) with natural, high specific mechanical performance and abundant functional groups to design a hydrogel as a drug-sustained release carrier, which conforms to the concept of green and sustainable development. Herein, we facilely extracted carboxylated lignocellulose nanofibrils (CLCNF) from bagasse via a deep eutectic solvent (DES) and mechanical defibrillation-based strategy. The CLCNF was crosslinked with poly(vinyl alcohol) (PVA) to obtain a nanocomposite hydrogel (PVA/CLCNF/B) whereupon the mechanical strength and drug release behavior were improved in the process. Consequently, the lignocellulose nanocomposite hydrogel presented a high compression modulus (3.92 MPa) and significant sustained-release effect with a release rate of 80.73 % after 336 h. The delivery behavior of the PVA/CLCNF/B composite hydrogel could be controlled by acidic pH conditions. The TH release kinetics of PVA/CLCNF/B hydrogel in different phosphate buffer saline (PBS) followed the Korsmeyer-Peppas model better, and the release of TH occurred through the Fickian diffusion mechanism. Importantly, in vivo experiments and histopathological studies showed that TH-loaded PVA/CLCNF/B hydrogel had a superior pro-healing rate. Overall, the incorporation of CLCNF into a hydrogel may have considerable potential as a drug delivery carrier for drug release and therapy. SynopsisAdding the CLCNF from bagasse into PVA dispersions obtained a hydrogel for pH-responsive drug delivery can accelerate wound healing.