The instruments arrangement of human-machine interface can directly influence the operation and efficiency of human-machine interaction in system. A novel instruments arrangement optimization method based on genetic algorithm was proposed. The biology heredity and evolution mode of genetic algorithm was used to search for the optimal or satisfying arrangement solution. Fitness function was constructed based on the principles of importance, frequency of use, relevance and operational sequence. Literal permutation encoding method was applied to represent the instruments arrangement. The optimization preserving strategy was used to enhance the search speed and to enlarge the width and depth of solution space. Finally, a case of instruments arrangement optimization proves that the arrangement optimization method is effective.