Potential difference in large grounding grid has not been concerned so far. By simulating analysis of a serious fault of the 500 kV breaker mis-operation during a 500 kV current transformer grounding fault in Pannan Power Plant in Guizhou province, the paper points out that abnormal high ground potential difference would likely interfere the signals in secondary control cable, cause secondary system relay protection mis-operation, and lead to a latent accident extension. A corresponding solution to reduce grounding grid potential is presented to reduce the risk of mis-operation or failure to operate. The scheme is suitable for both of the optimizing design and safety evaluation of large grounding grid of power plant, converter station or substation. To adapt to the developing requirements for grounding grid safety and streamline, single index that focuses only on grounding impedance should be discarded, and multiple safety indices should be attended to, such as ground potential rise, potential difference within grounding grid, step voltage and touch voltage.