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In this study, an inversion-based robust feedforward-feedback two-degree-of-freedom (2DOF) control approach is proposed to improve the tracking performance and robustness for multi-input multi-output (MIMO) systems with uncertainty. The proposed approach enhances trajectory tracking precision by robust-inversion feedforward control and combats the adverse effects caused by system uncertainty, coupling and disturbance by H∞ mixed sensitivity robust MIMO feedback control. The main contributions of this paper are as follows: (i) a combination of robust diagonal dominance-based static pre-compensation and inversion-based robust feedforword-feedback 2DOF control, (ii) extending the single-input single-output (SISO) robust-inversion-based feedforward control to MIMO system by introducing the optimal coefficients which not only consider the uncertainties of diagonal transfer functions, but also take the non-diagonal elements in MIMO transfer function matrix into account, (iii) a systematic integration of H∞ mixed sensitivity robust feedback control and inversion feedforward control. A numerical example and simulation results illustrate a better performance obtained by the proposed control approach compared with H∞ mixed sensitivity robust feedback control and 2DOF control approach combined with the regular SISO robust-inversion-based feedforward control and robust feedback control.