For design of the multi-chiller system, the configuration can be optimized that the system is high efficiency when it is operated under frequent load and operation condition in one year. Base on this idea, the paper presents a novel strategy of optimal configuration of multi-chiller system. The high hour-density range of annual load distribution and the high-efficiency region of combination of chillers are presented respectively, and their obtaining methods are developed. The overlap index is defined to evaluate the overlap between the high-efficiency region and high hour-density range, and it is maximized for the proposed optimal configuration strategy. GA is improved and employed for optimization. The proposed optimal configuration strategy is validated in a real multi-chiller system. The results show that the optimal configuration configured by the proposed strategy can improve annual Energy Efficiency Ratio (EER) about 5 % comparing with the original configuration of the real system. The configurations using equivalent strategy and typical non-equivalent strategy are compared, and the results show that both of hourly COP and annual EER of the configuration of the proposed strategy are better than them. 50 random configurations enumerated from chiller candidates are also compared. The results show that the overlap index is strongly correlated to annual EER, and it can be taken as optimization object for optimal configuration. Improved GA is compared with original GA, and the results show that of computation time cost can be reduced more than 60 % by use of Improved GA. The validation results show that the proposed strategy can obtain the optimal configuration of multi-chiller system directly from chiller candidates.