The natural environment affects the construction of desert highways. Conversely, highway construction affects the natural environment and puts the ecological environment at a disadvantage. To satisfy the variety and hierarchy of desert highway construction and discover the spatio-temporal distribution of the natural environment and its effect on highway construction engineering, an assessment of the natural regional divisions of desert highways in China is carried out for the first time. Based on the general principles and method for the natural region division, the principles, method and index system for desert highway assessment is put forward by combining the desert highway construction features and the azonal differentiation law. The index system combines the dominant indicator and four auxiliary indicators. The dominant indicator is defined by the desert’s comprehensive state index and the auxiliary indicators include the sand dune height, the blown sand strength, the vegetation coverage ratio and the annual average temperature difference. First the region is divided according to the dominant indicator. Then the region boundaries are amended according to the four auxiliary indicators. Finally the natural region division map for desert highway assessment is presented. The Chinese desert highways can be divided into three sections: the east medium effect region, the middle medium-severe effect region, and the west slight-medium effect region. The natural region division map effectively paves the way for the route planning, design, construction, maintenance and ongoing management of desert highways, and further helps environmental protection.