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The present-day Tibetan plateau, which is the largest highland on Earth, formed primarily due to the India-Asia collision since 50-60 Ma. The development of the plateau has been associated with the Cenozoic development of two large intra-plateau sedimentary basins in north-central Tibet: the Qaidam and Hoh Xil basins to the north and south of the Eastern Kunlun Range, respectively. We conducted an integrated study of these two basins and the Eastern Kunlun Range that separates them to understand the timing and mechanisms of their development in order to decipher the growth and uplift history of the plateau. Crustal shortening in the Fenghuoshan-Nangqian and Qilian Shan-Nan Shan thrust belts initiated no later than the early Eocene, which formed the northern and southern boundaries of the combined Hoh Xil and Qaidam basins in central Tibet. The distinct two-stage development of the Hoh Xil basin suggests emergence of a topographic barrier between the Hoh Xil basin in the south and Qaidam basin in the north in the early Neogene, which is supported by the existing and new apatite fission-track data from the Eastern Kunlun Range that suggest rapid cooling after ca. 20 Ma. Previous and newly collected geochronological, petrological, and thermochronological data are best interpreted in the context of the Paleogene Paleo-Qaidam hypothesis, which requires Hoh Xil and Qaidam basins to have been parts of a single integrated basin during the early stage of the Cenozoic Tibetan plateau development.