Under the background of climate change and the intensification of human activities, the spatial pattern and changes of human settlements on the Qinghai-Tibet Plateau have attracted wide attention in the world. Based on the relationship between human and land, this research puts forward the framework of comprehensive assessment of human settlement quality in Qinghai-Tibet Plateau. According to the Sustainable Development Goals (SDGs), the regional assessment of “localization” needs of The Times, this paper constructs the Tibetan Plateau human settlement quality assessment index system based on the plateau climate characteristics and human health, and evaluates the Qinghai-Tibetan Plateau human settlement quality status from 2000 to 2020. The assessment results of this research show that: (1) the quality of human settlements on the Qinghai-Tibet Plateau gradually increased from west to east. The hinterland of the plateau, represented by Ali region and Qiangtang Plateau, is mostly uninhabited areas with poor living environment. In the eastern part of the Plateau, the quality of human settlements is relatively suitable compared with the whole Qinghai-Tibet Plateau, especially the area of Yarlung Zangbo river and its two tributaries, the Hehuang valley and the southeast margin of the valley. (2) From 2000 to 2020, the proportion of suitable areas for human settlements on the Qinghai-Tibet Plateau has increased, and the quality of human settlements has significantly improved. The non-suitable areas mainly distributed in the central and western part of the Qinghai-Tibet Plateau, decreased from 70.54% to 55.37%. And the suitable area gradually expanded in the eastern margin of Qinghai-Tibet Plateau, and the proportion of the area increased from 1.28% to 13.99%. (3) From the perspective of the change contribution of the sub-system, the improvement of the human settlement on the Qinghai-Tibet Plateau is mainly due to the development of human society and economy. Among them, the economic environment has the greatest impact on the improvement of human settlements, with a contribution rate of 41.25%, which is the main driving force for the development of human settlements in the plateau region. The social (25.08%) and health (29.31%) environment are important supports, while the change of natural environment tends to be stable as a whole. The research results can provide reference value for improving the scientific territorial spatial planning of the Qinghai-Tibet Plateau, promoting the improvement and upgrading of the human settlement quality on the Qinghai-Tibet Plateau, and supporting the ecological protection and high-quality social and economic development of the Qinghai-Tibet Plateau.teau, and supporting the ecological protection and high-quality social and economic development of the Qinghai-Tibet Plateau.