The complex spatial environment of underground commercial street spaces will affect users’ behavior and information needs. As a medium to coordinate the interaction between the underground commercial street space environment and people, guide signs can provide useful information for users. However, the visual saliency of guide signs is the fundamental premise for determining the transmission of information to users. Based on field research, this study identified and examined the factors influencing the significance of guide signs in underground commercial streets from the user’s perspective using the order relation analysis method (G1 method) and with the help of screen-based eye tracking and virtual reality (VR) eye-tracking technology, In addition, we explored the design relationship between critical influencing factors and the space between underground commercial streets, and the visual significance of the differences between each important influencing variable. The study showed that the set position, set height, and design color of underground commercial street guide signs are essential factors in their visual prominence. The prominence was more significant when the position of guide signs was located in the middle and upper area of the space, and the prominence was more significant when the set height was 2.56~2.75 m and 3.12~3.31 m. This study can provide data and theoretical support for the visual saliency design of underground commercial street guide signs and provide a reference for the humanized design of underground commercial street guide signs for public facilities in cities.