Plant species diversity was surveyed in the northern Gaoligong Mountains of western Yunnan, China, from 1990 to 2006. During the floristic surveys of seed plants, 2514 native species and 302 varieties (or subspecies) belonging to 778 genera in 171 families were recorded. We also found that 12 families are endemic to eastern Asia, 14 genera and 1232 taxa are endemic to China, and 132 taxa are endemic to the northern Gaoligong Mountains. According to the International Union for Conservation of Nature (IUCN) Red List Categories and Criteria, 25 threatened taxa identified in the survey are endemic to this region. The flora is rich because of the role the northern Gaoligong Mountains played as a center of species diversification during the uplift of the eastern rim of the Tibetan Plateau in the Quaternary and as a refuge during the last glacial maximum. Unfortunately, this biodiversity faces massive threats because of the combined effect of habitat destruction or fragmentation and overexploitation of natural resources. Taking into consideration that human population growth will further increase pressure on this biodiversity in the near future, we suggest that conservation priority be given to the endemic plants, as well as to the habitats of primarily evergreen broad-leaved forest, coniferous broad-leaved mixed forest, and alpine shrub and meadows.