This work presents a detailed study for the systematic design and analysis of effective VPSA process control for the separation of methane-nitrogen mixture. A rigorous mathematic model of VPSA process was developed in prior to simulate the real VPSA process and to reflect its cyclic dynamic behaviours more exactly. Moreover, a powerful optimization of VPSA process for methane-nitrogen separation has been conducted to obtain a better base with superior performances for the exploration of design of VPSA controller. Subsequently, three kinds of disturbances scenarios have been introduced into VPSA system and the deterioration of process performances were significantly observed under open-loop operation. In order to get performance indicators back to the set point, PID and MPC controllers have been designed and tested. Results under close-loop operation demonstrated that the traditional PID controller can be used to regulate process performance but it would typically result in an over-saturation of target point with a slower response. In contrast, the MPC controller performed a more rapid and efficient response with less oscillatory behaviour in target tracking, which has indicated that it is more suitable for the regulation and control of VPSA process for methane-nitrogen separation. (C) 2019 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.