From the social background about the depletion of fossil fuels, global warming and emission reduction of carbon dioxide, there is growing international interest in hydrogen energy. To create a society based on hydrogen energy in the near future, it is necessary to clarify the influence of hydrogen on the mechanical, physical and chemical properties of the materials used for hydrogen energy systems. The rubber seals used for hydrogen equipment are repeatedly exposed to the high-pressure gas which has the change in rapid pressure and the wide range of temperature. In our previous study, the cyclic exposure of a rubber O-ring to high-pressure hydrogen gas caused internal cracks; then, raised hydrogen leakage. The occurrence of the internal cracks is considered to be influenced by several factors, such as material, pressure, temperature, and decompression rate. In this study, sensitive factors for the fracture of rubber O-rings were evaluated in terms of the L18 orthogonal experiment by high-pressure durability tester, which enables the rubber O-rings to expose repeatedly high-pressured hydrogen gas at arbitrary test conditions. The sensitive factors for high-pressure hydrogen gas seal were clarified from the graph of fractional effects and table of variance analysis.