This is the first in a series of papers describing the optimal design method for a digital human-computer interface of a nuclear power plant (NPP) from three different points based on human reliability. The purpose of this series is to propose different optimization methods from varying perspectives to decrease human factor events that arise from the defects of a human–computer interface. The present paper mainly discusses the optimization method for the layout of monitoring units. The layout of relative positions among different functional blocks in a digital human–computer interface influences the time required to search information. The risk of an event increases with increases in the time required to search for information because of the limited time available during a nuclear emergency. To avoid the risk of such an event, the authors propose an optimization method for the layout of monitoring units based on human reliability for a digital human–computer interface of a NPP. In the optimal design process, the authors propose a linear reversal genetic hybridization method that uses the Bayesian method as an adaptive function and takes human reliability as the optimized criterion. To quantitatively obtain the probability of human reliability, the authors use dynamic simulative functions including time and human factors. Finally, an experiment is conducted. The results indicate that the linear reversal genetic hybridization method has good stability and sensitivity and that the proposed optimization method has good accuracy and convergence.