The number of express boxes worldwide exceeded 170 billion in 2021, and, from several regions in China, tested positive. Therefore, it is important to study the transmission of viruses through express boxes. In this paper, we establish a model of express box virus transmission based on comprehensive consideration of environmental factors, such as temperature, disinfection, humidity, virus release intensity, and volume of vehicle, to study the transmission of express box virus, and explore the spatial and geographic spread variation of express box viruses in China. Several important findings emerged from the study, including: (1) Disinfection can prolong the spread of viruses in the express box for ≥21 h; (2) For every 1 °C rise in temperature, the infected time can be prolonged by ≥1.2 h, and for every 10% rise in relative humidity, the virus transmission time can be prolonged by ≥1.32 h; (3) In an environment suitable for virus transmission, when loaded with 1000, 2000, 4000 express boxes, areas where the express delivery time exceeds 22.56, 18, 14.64 h will face the risk of all the boxes in the carriage being infected. These findings could help public health departments prevent the risk of virus transmission from express boxes.