Advanced feedback control for optimal operation of mineral grinding process is usually based on the model predictive control (MPC) dynamic optimization. Since the MPC does not handle disturbances directly by controller design, it cannot achieve satisfactory effects in controlling complex grinding processes in the presence of strong disturbances and large uncertainties. In this paper, an improved disturbance observer (DOB) based MPC advanced feedback control is proposed to control the multivariable grinding operation. The improved DOB is based on the optimal achievable H-2 performance and can deal with disturbance observation for the nonminimum-phase delay systems. In this DOB-MPC advanced feedback control, the higher-level optimizer computes the optimal operation points by maximize the profit function and passes them to the MPC level. The MPC acts as a presetting controller and is employed to generate proper pre-setpoint for the lower-level basic feedback control system. The DOB acts as a compensator and improves the operation performance by dynamically compensating the setpoints for the basic control system according to the observed various disturbances and plant uncertainties. Several simulations are performed to demonstrate the proposed control method for grinding process operation.