Based on two chloroplast DNA sequences, psbA-trnH and trnT-trnF, phylogeographical patterns of a desert shrub, Ephedra przewalskii, were examined across most of its geographic range in northwestern China. A total of sixteen haplotypes were detected. There was a common haplotype in each basin, that was haplotype A in Tarim Basin, haplotype G in Junggar Basin, and haplotype M in Qaidam Basin. Genetic variance mainly occurred among populations, geographic regions, and eleven geographic groups subdivided by SAMOVA analysis. E. przewalskii likely had a smaller and more fragmented geographic range during the Last Glacial Maximum, which was determined based on ecological niche modelling. Three groups of E. przewalskii populations were detected to have experience range expansion, and this was based on significant values of Fu's FS, Tajima's D, and unimodel mismatch distributions. The cold and dry climate during the glacial period of the Quaternary is postulated to have been a driver for significant genetic isolation and divergence among populations or groups in E. przewalskii, whereas the warmer and wetter climate during the interglacial period is speculated to have provided favourable conditions for range expansion of the species.