A system for the safe coupling of a re-usable bag to a banknote handling and storing machine, the system includes a bag container, having an upper rigid mouth, of a flexible bag permanently fixed to the rigid mouth and of a lid for closing the rigid mouth. The system also includes a bag-holding frame, suitable for being stably fixed to a safe structure of the machine, for supporting and hooking the bag container when placed inside the machine to be filled in with the banknotes, is provided with coupling and hooking electromechanical components between the bag container and the bag-holding frame. The lid for closing the rigid mouth is further provided with an element suitable to allow, on command, the banknotes passing from the machine to the bag through the closed lid when the bag container is correctly inserted inside the machine.