The invention relates to a positioning device of a large beam slide block, which comprises a pair of screw rods which are fixedly connected with the top surface of the slide block, a locking seat which is fixedly connected with a machine body above the slide block, a locking pin and a locking pin drive mechanism; the locking seat is provided with a middle hole, and the wall of the locking seat hole is provided with a locking pin hole; the screw rods are movably connected with the locking seat through the middle hole, the locking pin is arranged on the side surface of the locking seat and is movably connected with the locking seat through the locking pin hole, the lower part of the screw rods is provided with a groove which is matched with the top end of the locking pin, and the locking pin drive mechanism is connected with the locking pin. After the slide block is automatically locked, the locking device can protect the machine and device and can protect the personnel when replacing the mould.