In this paper, a new approach towards input-output pairing for an unstable system has been proposed. First, it is demonstrated that the previous method of input-output pairing for unstable plants cannot find appropriate pairs as it only checks necessary conditions for stability and integrity. Then, a new approach using relative error matrix and genetic algorithm for finding appropriate pairs in unstable systems is proposed. As it is shown, this approach takes into consideration both static and dynamic information of plant in measuring interaction. Finally, the accuracy of proposed method is demonstrated by an example and closed loop simulation.