The interaction of recent orographic uplift and climate heterogeneity acted as a key role in the East Himalaya-Hengduan Mountains (EHHM) has been reported in many studies. However, how exactly the interaction promotes clade diversification remains poorly understood. Here, we both studied genetic structure of the chloroplast trnT-trnF region and 11 nuclear microsatellite loci in Hippophae gyantsensis and examined what role geological barriers or ecological factors play in the spatial genetic structure. The results showed that this species had a strong east-west phylogeographic structure, with several mixed populations identified from microsatellite data in central location. The intraspecies divergence time was estimated to about 3.59 Ma, corresponding well with the recent uplift of the Tibetan Plateau. Between the two lineages there was significant climatic differentiation without geographic barriers. High consistency between lineage divergence, climatic heterogeneity and Qingzang Movement demonstrated that climatic heterogeneity but not geographic isolation drives the divergence of H. gyantsensis, and the recent regional uplift of the QTP, as the Himalayas, create heterogeneous climates by affecting the flow of the Indian monsoon. The east group of H. gyantsensis experienced population expansion c. 0.12 Ma, closely associated with the last interglacial interval. Subsequently, a genetic admixture event between east and west groups happened at 26.90 ka, a period corresponding to the warm inter-glaciation again. These findings highlight the importance of the Quaternary climatic fluctuations in the recent evolutionary history of H. gyantsensis. Our study will improve the understanding of the history and mechanisms of biodiversity accumulation in the EHHM region.