Human settlements' suitability in ecologically fragile regions is critical for sustainable development and ecological security. However, comprehensive assessments that integrate multiple natural environmental factors are insufficient. Here, we establish a human settlements suitability index (HSI) to assess human settlements' suitability on the Qinghai-Tibet Plateau, including Relief Degree of Land Surface (RDLS), Temperature-Humidity Index (THI), Land Surface Water Abundance Index (LSWAI), and Land Cover Index (LCI). The results show that: (1) The RDLS of the Qinghai-Tibet Plateau was generally high, reflecting elevated terrain and steep topography, with strong regional variation. THI increases from the northwest arid region to the southeast, while high LSWAI and LCI were concentrated and show a zonal distribution. (2) The HSI ranged from 0.07 to 1, with seven suitability types. Low-suitability was distributed in the Kunlun, Gangdise, Himalayas, and the northern and southern parts of the Tibetan valleys. Mid-suitability appeared in the Sichuan-Tibet Alpine Canyon, while high-suitability was concentrated in the northeast (Qaidam Basin, Qilian, Hengduan Mountains), the west (Menyu), and the Qaidam Basin. (3) Low-suitability covered over 70% of the Qinghai-Tibet Plateau but hosts only 20% of the population. Mid-suitability occupied about 20% of the land, yet contained nearly 70% of the population. High-suitability (HSI > 0.7) areas were limited but concentrated populations in the Qaidam Basin, southern Tibetan valleys, and eastern Sichuan-Tibet Alpine Valleys. Future development should target these high-suitability regions to support sustainable population growth and reduce land pressure. These findings provide a scientific basis for regional planning, population distribution, and ecological security on the Qinghai-Tibet Plateau.