Comprehensive geographical division systematically reflects the regional differentiation of nature. However, current research still lacks an integrated consideration of multiple factors, including biotic, abiotic, and geomorphologic. At present, the construction of nature reserve system with national parks as the mainstay has achieved fruitful results. It is urgent to put forward a zoning plan that takes into account both natural geographical characteristics and biological differentiation pattern from a regional perspective. Taking comprehensiveness, combination of zonality and non-zonality, combination of biological factors and abiotic factors as the basic principles of zoning. Adopting five indexes such as heat, moisture, soil, vegetation, and animals' geographical distribution. Through the Self-Organizing Feature Map (SOFM) comprehensive cluster, based on cluster results, and combined with the boundary of mountain range and the integrity of landform zoning units was delineated in the top-down principle. Corrected on the basis of the Xinjiang territory- wide field scientific investigation results and satellite remote sensing three-dimensional imagery, while taking full account of the distribution of natural protected areas in Xinjiang. It ensures the objectivity, scientificity, systematicness, accuracy, and applicability of zoning. Finally, the comprehensive geographical regionalization of Xinjiang was divided into four levels, including 5 zones (first level zoning), 11 regions (second level zoning), 21 subregions (third level zoning), and 48 areas (fourth level zoning). In which, the first level zoning was in harmony with the topographic distribution pattern of "three mountains and two basins" in Xinjiang. It was divided into the Altai Mountains Ⅰ, the Junggar Basin-Beita Mountain Ⅱ, the Tianshan Mountains Ⅲ, the Tarim Basin-Tuha Basin Ⅳ, and the Kunlun Mountains-Altun Mountains Ⅴ. This study generalized the natural protected areas and main protected objects in natural conservation geographical unit. The zoning scheme was in good agreement with the distribution of nature protected areas in Xinjiang. The vast majority of natural protected areas do not cross natural conservation geographical subregion, and the geographical distribution of species in each natural conservation geographical unit was also relatively non-isolated. Natural protected areas within the same natural conservation geographical unit can be organized into clusters of natural protected areas aimed at protecting keystone species, umbrella species, or flagship species to building a regional network of natural protected areas and improving ecosystem connectivity. The zoning scheme will play an important guiding role in biodiversity protection, natural protected area system with national parks as the mainstay and habitat corridor construction in Xinjiang. Furthermore, it also provides theoretical basis and reference for the comprehensive geographical zoning of natural conservation in other provinces and even the whole country.