The interactions between input/output variables are a common phenomenon and the main obstacle encountered in the design of multi-loop controllers for interacting multivariable processes. In this study, a novel method for the independent design of multi-loop PI/PID controllers is proposed. The idea of an effective open-loop transfer function (EOTF) is first introduced to decompose a multi-loop control system into a set of equivalent independent single loops. Using a model reduction technique, the EOTF is further approximated to the reduced-order form. Based on the corresponding EOTF model, the individual controller of each single loop is then independently designed by applying the internal model control (IMC)-based PID tuning approach for single-input/single-output (SISO) systems, while the main effects of the dynamic interactions are properly taken into account. Several illustrative examples are employed to demonstrate the effectiveness of the proposed method. (C) 2010 Elsevier Ltd. All rights reserved.