A system for the safe coupling of a re-usable bag to a banknote handling and storing machine includes a bag container, having a rigid upper port and a flexible bag permanently fixed to the rigid port, a lid, designed to be inserted onto the rigid port for closing the bag container when the filling operations are terminated, and a bag-holding frame. The bag-holding frame is 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 with the banknotes. The system is provided with first coupling and hooking electro-mechanical components between the bag container and the bag-holding frame and with second coupling and hooking electro-mechanical components between the lid and the bag container. The first and second coupling and hooking electro-mechanical components are interconnected with a control unit to enable the respective functions.