A novel method of incorporating generalized predictive control (GPC) algorithms based on quantitative feedback theory (QFT) principles is proposed for solving the feedback control problem of the highly uncertain and cross-coupling plants. The quantitative feedback theory decouples the multi-input and multi-output (MIMO) plant and is also used to reduce the uncertainties of the system, stabilize the system, and achieve tracking performance of the system to a certain extent. Single-input and single-output (SISO) generalized predictive control is used to achieve performance with higher performance. In GPC, the model is identified on-line, which is based on the QFT input and the plant output signals. The simulation results show that the performance of the system is superior to the performance when only QFT is used for highly uncertain MIMO plants.