The hydrogen production from natural gas has advantages of low investment, low carbon emission, and high hydrogen production rate. This paper briefly describes the technical overview of hydrogen production from natural gas reforming and identifies its risk factors. According to the dangerous characteristics of high reaction temperature, easy leakage of reaction medium, flammability, and explosion in the process, the intrinsic safety of the process is discussed in combination with relevant research and industrial experience. The safety requirements of key equipment and materials are introduced in detail, followed by the optimization methods of process safety that can be taken in the engineering process. Besides, the accident prevention measures for emergency shutdown and fire explosion are summarized. Finally, the future research demands are put forward from the perspective of research and development, which is instructive for the safe hydrogen production from natural gas in the future.