The invention discloses a manufacture method of a multi-baffle large-aperture box frame. The method comprises the steps of firstly, reliably connecting positioning bases and limiting blocks, ensuring that side surfaces of the positioning bases and the limiting blocks are adhered, loading the positioning bases and the limiting blocks into baffle inner holes integrally, then welding the limiting blocks with baffle bearing seats in a spot welding way, secondly, establishing lines on a combined platform to determine positions of all baffles, ensuring that a core shaft penetrates through all the positioning bases, fixing the positions of the positioning bases separately through positioning pins, connecting the positioning bases with the core shaft, thirdly, welding all process supports with inner holes of all the baffles in a spot welding way in weight reduction notch space positions arranged on the positioning bases, fourthly, cutting welding lines of the limiting blocks and the bearing seats, laying the limiting blocks in directions perpendicular to disc diameters of the positioning bases, gradually withdrawing the positioning bases and the core shaft, welding a frame body, welding connecting plates among all the baffles, and fifthly, performing thermal aging on the frame body integrally, and then removing all the process supports. The method improves the frame body combination accuracy and the operating efficiency.