For long-distance natural gas pipes crossing highway, the changing load of vehicles is the most important and frequently acting-live load on buried pipes, which poses a serious threat to the integrity of the pipe. This study has designed and built a buried pipe stress test experimental system. The experimental system is mainly composed of a sealed pipe, an air compressor, and a stress-strain testing system. In this study, a total of 24 sets of stress test experiments are carried out. The research conclusions are as follows. The maximum stress of the pipe occurs at the 12 o’clock position of the pipe when the vehicle load is rolled at the middle. The increase in vehicle load results in an increasing pipe stress value. Both of the vehicle speed and the internal pressure play a certain role in protecting the pipe. After carrying out a real experimental case via Sinopec’s natural gas pipe crossing the highway, we have found that it can withstand the rolling load of a heavy vehicle of 78t, when the L325 steel pipe section that crossing the Grade-4 highway has a buried depth of 0.8m, a diameter of 355.6 × 5.6mm, and a internal pressure of 1.03MPa.