Abstract: The paper proposes a new control strategy to apply in the field of pressure controller of once-through steam generator. The strategy is distributed and multiple input and output coupling Artificial immune control strategy which is based the thought of decentralized control of the distributed control system, the immune mechanism of B-cell co-operating with T-cell, and the biological immune mechanism of antigens and antibodies interacting. In order to verify the control strategy, simulation experiment has been carried out in a simulator of fast reactor. The simulation results show that the new control strategy has small overshoot and shorter steady time compared with conventional PID control strategy, and it can effectively improve the dynamic operating characteristics of pressure and related parameters of once-through steam generator.