Abstract: A mathematical model of controller parameter tuning based on immune theory is established. Antibody, antigen, and affinity of the parameter tuning problem are defined. The process of parameter tuning based on immune principles is discussed in detail. The method is used to optimize the three parameters of proportion-integral-derivative (PID) controller for the control of high-order process, large time delay process, and non-minimum phase process. The results compared with some other tuning methods show the effectiveness of the proposed method is effective.