By taking into account the topology characteristics of power substations or plants in the relay coordination of the high-voltage transmission system， the operation mode variation in the power substations or plants can be thought of as an integral unit with different impedance parameters. Two types of sensitivity factors are derived that demonstrate the relationship between the fault current or coordination coefficients and different operation modes of different substations or plants. The operation mode of substations or plants with great impact on the setting of relays will be considered in the relay coordination. Numerous ineffective operation modes are excluded based on the sensitivity factor identification in advance. The results of engineering examples show the effectiveness and practicability of the proposed method in improving the accuracy of setting and efficiency of the relay coordination software.