Dystrophic epidermolysis bullosa (DEB) is a rare genetic skin disease characterized by blisters and ulcers on the skin and mucosa after minor friction. The risk of invasive squamous cell carcinoma on the unhealed ulcers increases with age. Tracheal intubation during general anesthesia may induce tracheal stricture due to blister formation and/or scarring in DEB patients and cause severe airway obstruction. There is no consensus for handling DEB patients' fragile mucosa and skin during general anesthesia. We report an adult DEB patient who received two operations under different general anesthesia methods. The experience from this particular patient and her response to anesthesia may provide a satisfactory guide to avoid complications and improve the outcome for DEB patients receiving general anesthesia.