The invention relates to a U-shaped steel and concrete combined orthogonal-diagonal spatial grid box type structure. Open web girders of a building floor are rigidly connected with a reinforced concrete grid type frame column at the periphery of the open web girders; the periphery of the building floor is an isosceles triangle grid, and the middle along the periphery at an included angle of 45 degrees is a square open web grid; the relation between the dimension a of the right-angle sides of the isosceles triangle at the periphery and the hypotenuse length a1 of the isosceles triangle is a=a1*sin (45 degrees), the building floor is formed by the connection of a lower chord and an upper chord via a reinforced concrete shear key, and the lower chord is formed by a U-shaped steel member and a reinforced concrete layer arranged in a U-shaped steel member groove. According to the structure, the concrete crack development of the lower chord of the floor is controlled, the periphery of the open web floor and the reinforced concrete grid type frame column are rigidly connected, when the span is greater than 30 m, the grids of the lower chord enable the internal force to be uniformly distributed, the hysteresis performance and the ductility of the structure are improved, the thickness of the floor is reduced, the thickness of the storey is further reduced, the storey height of the building is reduced, and the engineering cost is lowered.