The invention relates to an opening anti-fatigue arrangement structure and method of ship double bottoms and belongs to the technical field of ship upright arrangement structures. The opening anti-fatigue arrangement structure of the ship double bottoms is characterized in that square holes are formed in the positions, located on the left side and the right side of an upright, at the inner bottom of the ship double bottoms correspondingly and each internally provided with a rectangular metal box body, and the side faces of the rectangular box bodies are fixed to watertight ribbed plates between the ship double bottoms and the side face of the upright in a welded mode. According to the opening anti-fatigue arrangement structure and method of the ship double bottoms, flexible connecting of the upright and the double bottoms of the ship is achieved, and the phenomenon that the local stress is overlarge when the box bodies are slightly transformed is avoided; and the anti-fatigue strength of the connecting positions of the upright and the double bottoms are greatly promoted, and reliability is promoted.