A mainframe cooling structure is disclosed to include a body, which has a side cover and a ventilation grille at the side cover for letting air in and out, a circuit board, which is fixedly mounted inside the body and has an electronic device that produces heat during operation, and a cooler module, which includes a heat sink attached to the electronic device, a fan holder provided at the top side of the heat sink, and two fans mounted in the fan holder and aimed at different parts of the ventilation grille for drawing outside cooling air toward the heat sink and drawing inside hot air out of the body.