With the changing of production types, taking setup time into consideration is getting more and more important for industrial schedulers. Therefore, in this research, we explores the single machine scheduling problem with minimizing the total absolute deviation and setup cost where setup times are sequence dependent. Genetic algorithm is applied to search the optimal or near-optimal solutions in this research owing to its outstanding parallel searching capability. Moreover, through experimental design and statistical analysis, genetic algorithm is verified to receive comparative improvement. Besides the above-mentioned results, this research investigates the optimal designs of parameters used in the genetic algorithm. We discuss the effect of number of chromosomes per population, crossover rate, mutation rate, number of generations and propose the difference between variable mutation rate and fixed mutation rate. Algorithm with variable mutation rate results in superior solutions, but it is difficult to convergent state. On the other hand, the convergence of fixed mutation rate is superior to variable mutation rate, and the solution quality is more robust than variable mutation rate.