For some complex systems with several controlled variables and with interaction between these controlled variables, one complex mathematical model is established to include lots of elements in the control matrix. In order to reduce the number of elements in the control matrix and increase real-time property in designing the unknown controllers, an idea of non-interaction property is introduced to simplify our mentioned closed loop system with many variables. To achieve the non-interaction property, some conditions are derived to guarantee one controlled input only influences one output. Based on this simplified model, the prediction error method coming from system identification field is applied to design the optimal controllers. The advantage of our prediction error method is that the optimal controller is a constant ratio of two polynomials. Finally one simulation example confirms our theoretical results.