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Thawing permafrost has affected the structural integrity of buried warm pipelines in cold regions and poses an ongoing threat in the context of climate change. Therefore, characterizing variation in the engineering properties of pipeline foundation permafrost and its effect on the mechanical behavior of pipeline is important. In this paper, the ground temperature distributions around a buried warm pipeline and mechanical response of the pipeline to differential thaw settlement of foundation permafrost are investigated using thermal–mechanical sequential coupling simulation, based on the observational data collected from a selected monitoring site along the China-Russia crude oil pipelines in northeastern China. The results indicate that the thaw-induced settlement of pipeline foundation permafrost develops quickly with the formation and expansion of the thaw bulb in the first 10 years, and then increases slowly when the thaw bulb extends to the weathered granite. Differential thaw settlement will cause a significant change in the deformation and stress of the pipeline near the interface of strong and weak thaw settlement zones. When the length ratio of strong and weak thaw settlement zones is 1, the maximum stress of the pipeline with a thickness of 16 mm is approximately 45% of the allowable stress of X65 steel, and the pipeline remains safe for 30 years. However, the potential failure of the pipeline should be considered due to the continued ground thawing and warming and pipe material aging. Forthcoming research on this topic is needed to evaluate more carefully the structural integrity of buried pipelines in cold regions. [ABSTRACT FROM AUTHOR]