A main drive high-pressure sealing system for shield machine comprising an air cushion bin, an oil and gas sealing chamber, a compressed air input port, a first positive pneumatic regulating valve and a first negative pneumatic regulating valve, wherein an inlet of the compressed air input port is configured to connect with an air source, an outlet of the compressed air input port is connected to an inlet of the first positive pneumatic regulating valve, an outlet of the first positive pneumatic regulating valve is connected to an inlet of the first negative pneumatic regulating valve and the oil and gas sealing chamber, and an outlet of the first negative pneumatic regulating valve is connected to an exhaust pipeline; a positive pressure detection terminal of the first positive pneumatic regulating valve and a positive pressure detection terminal of the first negative pneumatic regulating valve are both connected to the air cushion bin; a negative pressure detection terminal of the first positive pneumatic regulating valve and a negative pressure detection terminal of the first negative pneumatic regulating valve are both connected to the oil and gas sealing chamber; when pressure difference between the air cushion bin and the oil and gas sealing chamber is greater than or equal to a first preset value, the first positive pneumatic regulating valve is opened, and the first negative pneumatic regulating valve is in a closed state; and when the pressure difference between the air cushion bin and the oil and gas sealing chamber is less than or equal to a second preset value, the first negative pneumatic regulating valve is opened, and the first positive pneumatic regulating valve is in a closed state. an inlet of the compressed air input port is configured to connect with an air source, an outlet of the compressed air input port is connected to an inlet of the first positive pneumatic regulating valve, an outlet of the first positive pneumatic regulating valve is connected to an inlet of the first negative pneumatic regulating valve and the oil and gas sealing chamber, and an outlet of the first negative pneumatic regulating valve is connected to an exhaust pipeline; a positive pressure detection terminal of the first positive pneumatic regulating valve and a positive pressure detection terminal of the first negative pneumatic regulating valve are both connected to the air cushion bin; a negative pressure detection terminal of the first positive pneumatic regulating valve and a negative pressure detection terminal of the first negative pneumatic regulating valve are both connected to the oil and gas sealing chamber; when pressure difference between the air cushion bin and the oil and gas sealing chamber is greater than or equal to a first preset value, the first positive pneumatic regulating valve is opened, and the first negative pneumatic regulating valve is in a closed state; and when the pressure difference between the air cushion bin and the oil and gas sealing chamber is less than or equal to a second preset value, the first negative pneumatic regulating valve is opened, and the first positive pneumatic regulating valve is in a closed state.