Enzymatic degradation of demineralized collagen matrix seriously impairs durable resin-dentin bonding. In this study, we evaluated the effect of nordihydroguaiaretic acid (NDGA)-modified etchant on the resistance to enzymatic degradation and mechanical properties of demineralized collagen matrix. Dentin beams were randomly demineralized by following solutions: 1) 10% phosphoric acid (PhA) solution, 2) 10% dimethyl sulfoxide (DMSO)-PhA solution, 3) NDGA-modified etchant, and 4) proanthocyanidins (PA)-modified etchant. The demineralized dentin collagen was then digested by type I collagenase solution. The collagenase degradation resistance was evaluated by measuring loss of dry mass, hydroxyproline release, and elastic modulus change. The degradation rate and hydroxyproline release of dentin collagen treated with NDGA-modified etchant were significantly lower than those in the other groups (P < 0.001). The elastic modulus of dentin beams treated with NDGA-modified etchant did not increase significantly. However, after 48 h of collagenase degradation, the loss of elastic modulus of dentin beams treated with NDGA-modified etchant was significantly lower than that of the control group (P < 0.001). The NDGA-modified etchant could improve the resistance to enzymatic degradation of type I collagenase degradation, and the stability of the mechanical properties of dentin collagen. This proof-of-concept study validates the etch-and-crosslink technique that improves durability of dentin bonding through simultaneous dentin etching and collagen crosslinking. (C) 2017 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.