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Denisovans are members of a hominin group only known from fragmentary fossils genomically studied from a single site, Denisova Cave 1-3 in Siberia, and from their genetic legacy through gene flow into several low-altitude East Asian populations 4,5 and high-altitude modern Tibetans 6 . The lack of morphologically informative Denisovan fossils impedes our ability to connect geographically and temporally dispersed Asian fossil hominins and understand their relation to these recent populations in a coherent manner, including the Denisovan-inherited human adaptation to the high-altitude Tibetan Plateau 7,8 . Here we report a Denisovan mandible, identified by ancient protein analysis 9,10 , found in Baishiya Karst Cave, Xiahe County, Gansu Province (China), on the Tibetan Plateau. We determine the mandible to be at least 160 thousand years old through U-series dating of an adhering carbonate matrix. It is the first direct evidence of this hominin group outside the Altai Mountains, and provides unique insights into Denisovan mandibular and dental morphology. Our results indicate that archaic hominins occupied the Tibetan Plateau in the Middle Pleistocene and successfully adapted to high-altitude hypoxia environments much earlier than the regional arrival of modern Homo sapiens.