The temperature-dependent enzymatic degradation of semi-IPN hydrogels consisting of dextran grafted with thermo-responsive chains (lower cloud point) and a thermo-responsive crosslinked matrix (higher cloud point) was examined. Enzymatic degradation of the semi-IPN hydrogel was significantly inhibited below the lower and above the higher cloud point. Only between both cloud points, enzymatic degradation proceeded. The designed semi-IPN hydrogel is therefore advantageous to achieve enzymatic degradation at a specific temperature range.