The invention relates to a method for calibrating a nuclear instrumentation system by adopting accurate flow of a main loop. The method comprises the following steps: 1, acquiring flow signals at multiple positions of a loop in a loop system and a rotating speed signal value Vpp of a main pump of the loop system; 2, selecting high-order or low-order signals in the acquired flow signals at multiple positions to serve as a flow selection signal value A; 3, calibrating the flow selection signal value A through a flow transfer function, and acquiring a flow calibration signal value A'; 4, acquiring a neutron fluence rate signal value B in the reactor, calibrating the neutron fluence signal value B through a neutron fluence transfer function, and acquiring a neutron fluence calibration signal value B'; 5, acquiring an average temperature signal value C of the loop system, calibrating the average temperature signal value C of the loop system through an average temperature transfer function of the loop system, and acquiring an average temperature calibration signal value C' of the loop system; and 6, acquiring the calibrated neutron fluence change ratio signal value D. According to the method, the reliability, safety and economical efficiency of the nuclear power plant are improved.