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 O-rings used in the high-pressure sometimes suffer from the decrease in durability due to decompression failure, which is influenced by several factors. From this viewpoint, sensitive factors for the durability of rubber O-rings were evaluated by using a L18 orthogonal array. A high-pressure durability tester, which enables the rubber O-rings to expose repeatedly high-pressure hydrogen gas at arbitrary test conditions, was employed. Of lower-limit pressure, upper-limit pressure, material, temperature, O-ring filling ratio, holding time at lower limit, holding time at upper limit, and decompression time, it was clarified that the material, temperature, O-ring filling ratio, and decompression time were sensitive factors from the graph of fractional effects and analysis of variance table.