Dressings are prone to adhering to new tissues, leading to secondary harm to the wound during dressing replacement. To address this issue, many strategies have been proposed to endow dressings with anti-adhesive functions. However, the introduction of exogenous agents or stimuli is always needed, and difficulty in achieving adaptive removal is also present. Herein, an endogenous gelatinase-responsive core-shell nanofiber membrane containing hydroxy-terminated polydimethylsiloxane (HTPDMS) was developed for anti-adhesion applications. The core-shell nanofiber membrane is created via coaxial electrospinning technique, where a mixture of gelatin and polycaprolactone (PCL) serves as shell layer and HTPDMS serves as core layer. In the presence of gelatinase, the gelatin component in shell layer is degraded, and many grooves are formed on the surface, which provide channels for the migration of HTPDMS with low surface energy, further forming a hydrophobic lubricating coating on the rough surface. This coating enhances the hydrophobicity of the membrane while significantly reducing its protein adsorption characteristics and adhesion to isolated tissues. Moreover, the current nanofiber membrane is highly cytocompatible with L929 mouse fibroblasts. This finding provides a proof-of-concept for an anti-adhesive nanofiber membrane for adaptive removal and demonstrates great potential for alleviating patient discomfort during dressing replacement and enhancing wound healing.