Current standards for designing Ω-ring welded sealing structures calculate bolt preload solely based on internal pressure, neglecting the influence of differential thermal expansion under temperature variations, which is particularly significant under low-pressure and high-temperature conditions. In this study, three materials commonly used for flanges and Ω-rings, such as 316L, SA336, and 16Mn, were selected for the Ω-ring welded sealing structure under low-pressure and high-temperature conditions. By employing numerical simulation methods, the influence of differential thermal expansion on the stress distribution within Ω-ring under low-pressure and high-temperature conditions was investigated. The results reveal that under low-pressure and high-temperature conditions, the variation of bolt load induced by differential thermal expansion constitutes a significant and non-negligible proportion of the initial preload. Furthermore, due to differences in material properties, when the thermal expansion of bolts exceeds that of flanges and Ω-ring, resulting in a negative expansion, compensation for the bolt load or correction of the initial preload is required.