Incorporating hydrogen into natural gas pipelines is an effective way to promote the large-scale utilization of hydrogen energy. The operational safety of hydrogen-blended natural gas is an unavoidable problem. In recent years, the preliminary theoretical research, analysis of the impact of the transmission process, terminal adaptability and low-pressure pilot tests on hydrogen-blended natural gas pipelines have been carried out at home and abroad, but the technical safety-related adaptation of the hydrogen-blended system has not been fully integrated with the characteristics of the long-distance pipeline system. Based on the physical properties of hydrogen and natural gas, the method for determining the key parameters of hydrogen-blended natural gas pipeline engineering design is discussed, and the impact of hydrogen-blended natural gas on the safety of key pipeline transportation processes is discussed in combination with the engineering design concerns, and relevant suggestions for engineering design are put forward. The research shows that the minimum ignition energy, the lower explosion limit and the Joule-Thomson effect of the mixed medium are reduced and the leakage trend is increased after the natural gas is blended with hydrogen; the post-leakage thermal radiation range and potential impact radius of hydrogen-blended natural gas decreases with increasing hydrogen blending ratio. The temperature, leakage volume flow rate, erosion index, leakage diffusion range and combustible gas detection index after the adiabatic release increase with the increase of hydrogen blending ratio. hence, attention shall be paid to the implementation of the project. The research results of this paper provide reference for the hydrogen-blended natural gas pipeline project in the future.