The Yalu Tsangpo River, the highest river in the world, originating from the Himalayas, is the most important international river in Tibet. Compared with rivers in normal elevation areas, the aquatic ecosystem of the Yalu Tsangpo River is unique due to its special topography and ecological conditions. Research about the macroinvertebrates in relation to environments is an important basis for scientific assessment of river ecology and sustainable utilization of water resource in the Yalu Tsangpo River. Field investigations were conducted at 14 sampling sections by using macroinvertebrates as indicators to assess the river ecology of the Yalu Tsangpo River during October 2009 - June 2010. Several alpha diversity indices were used to assess biodiversity of the sampled sections. A beta diversity index was calculated to evaluate the biodiversity of the whole sampled river reaches. From analyses of the assemblage composition of all samples, altogether 110 taxa of macroinvertebrates, belonging to 57 families and 102 genera, were identified from the Yalu Tsangpo River Basin. The maximum and average values of macroinvertebrate taxa richness in the main channel of the Yalu Tsangpo River were 29 and 19, respectively. The taxa richness in the tributary Nianchu River, was lower than that in the main channel. The maximum values of taxa richness in the tributaries: Lhasa, Niyang, and Palong Tsangpo rivers were 25, 33, and 36, respectively; and the average values were 21, 21, and 22, respectively, which were higher than those in the main channel. For different sampling sections, no large variance existed in taxa richness, while taxa composition and density of macroinvertebrates were very different. The beta diversity index of the Yalu Tsangpo River, was much higher than that in normal elevation rivers, indicating much higher heterogeneity of macroinvertebrates in the Yalu Tsangpo River. Macroinvertebrate assemblages of the 14 sections were clustered using Detrended Correspondence Analysis (DCA). The ordination diagram indicated that the main factors impacted macroinvertebrate assemblages of the Yalu Tsangpo River were river pattern, riverbed structures, bank structures, and flow conditions. Keeping stable step-pool systems, natural bank structures, and suitable flow velocity is in favor of conservation of river ecology of the Yalu Tsangpo River.