This paper addresses the hybrid flow shop (HFS) scheduling problem with unrelated parallel machines considering sequence and machine dependent setup times. The performance measurement used in this study is based on minimizing maximum completion time (makespan). Because of the complexity of the problem, a meta-heuristic based on the imperialist competitive algorithm (ICA) and the genetic algorithm (GA) has been used. To achieve reliable results, an experimental design has been developed to determine the incidence of the factors in the objective function which is applied in twelve instances. The efficiency of the meta-heuristic is compared with a model of mixed-integer programming validated in GAMS. The results of the study reveal that the meta-heuristic obtains equal or better solutions than those of the exact method for half of the instances.