The Hengduan Mountains region is considered to be an important reservoir and a differentiation center for temperate and alpine plants during the Cenozoic. To reveal the effects of extreme topography and climate on an organism's population genetic structure in this region, a phylogeographic study has been carried out for Ligularia vellerea. We sequenced two chloroplast DNA fragments, trnH-psbA and trnL-rpl32, for 157 individuals of 15 populations and a total of 14 haplotypes were identified. These haplotypes clustered into five clades and each of them was mainly distributed in the restricted regions. A strong phylogeographic structure of this species was detected (N ST = 0.851, G ST = 0.713; N ST > G ST , P < 0.01). The strong population differentiation in L. vellerea could be attributed to the repeated glacial/interglacial cycles during the Pleistocene, which has been further enhanced by restricted gene flow caused by the complicated topography in the Hengduan Mountains region that formed during the uplift of the Qinghai-Tibet Plateau.