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This paper considers group scheduling problem in hybrid flexible flow shop with sequence-dependent setup times to minimize makespan. Group scheduling problem consists of two levels, namely scheduling of groups and jobs within each group. In order to solve problems with this context, two new metaheuristics based on simulated annealing (SA) and genetic algorithm (GA) are developed. A design procedure is developed to specify and adjust significant parameters for SA- and GA-based metaheuristics. The proposed procedure is based on the response surface methodology and two types of objective function are considered to develop multiple-objective decision making model. For comparing metaheuristics, makespan and elapsed time to obtain it are considered as two response variables representing effectiveness and efficiency of algorithms. Based on obtained results in the aspect of makespan, GA-based metaheuristic is recommended for solving group scheduling problems in hybrid flexible flow shop in all sizes and for elapsed time SA-based metaheuristic has better results. [ABSTRACT FROM AUTHOR]