Abstract Pressure pipelines use pressure to transport gas, liquefied gas, and steam in the process of use. If there are defects in the pipeline, it is easy to leak or burst, and even cause secondary accidents. To ensure safety, it is necessary to inspect the pressure pipelines in use regularly. However, it is difficult for the pressure pipeline in use to empty the internal medium. Therefore, it is of great significance to inspect the defects of the industrial pressure pipeline under operating conditions. In this paper, X-ray testing experiments are carried out for weld defects of pipelines with the medium. Using the experimental data, multivariate polynomial regression equations of negative blackness and tube voltage, and other variables are established, which provides an effective tool for the formulation of the optimal process route for testing pressure pipelines containing medium.