The extreme environment of the Qinghai-Tibet Plateau (QTP) provides an ideal natural laboratory for studies on adaptive evolution. Few genome/transcriptome-based studies have been conducted on how plants adapt to the environments of the QTP compared with numerous studies on vertebrates. Crucihimalaya himalaica is a close relative of Arabidopsis with a typical QTP distribution, and is hoped to be a new model system to study speciation and ecological adaptation in extreme environments. In this study, we generated a de novo transcriptome sequence of C. himalaica, with a total of 49,438 unigenes. In a comparison with five related species, we identified 10,487 orthogroups shared by all six species and 4,286 orthogroups that contained a putative single-copy gene. Further analysis identified 487 extremely significantly positively selected genes (PSGs) in the C. himalaica transcriptome. Theses PSGs were enriched in functions related to specific adaptation traits, such as responses to radiation, DNA repair, nitrogen metabolism, and membrane stabilization. These functions are probably responsible for the adaptation of C. himalaica to the high radiation, depleted soil and low temperature environments on the QTP. Our findings indicate that C. himalaica has evolved complex strategies to adapt to the extreme environments on the QTP and provide novel insights into the genetic mechanisms of highland adaptation in plants.