The Yarlung Tsangpo Grand Canyon region is located in the frontal zone of the eastern Himalayan syutaxis, where neo-tectonics and seismicity are intensive and closely related to each other. In the region, two sets of fault structures have developed, striking NNE-NE and NWW-NW, respectively. Investigation shows that they differ markedly in terms of scope, property, active times and intensity. The NWW-NW trending faults are large in size, and most are thrust and thrust strike-slip faults, formed in earlier times. The NEE-NE-strike faults are relatively small in size individually, with concentrated distribution, constituting the NNE-trending shear extensional fault zone, which is relatively younger with evident late Quaternary activities. Strong earthquakes occur mainly in the areas or zones of intensive differential movement of the Himalayas, e.g. along the deep and large fault zones around the crustal blocks. Most earthquakes of M≥7.0 are closely related to tectonics, where large-scale Holocene active faults are distributed with complicated fault geometry, or the faults of multiple directions intersect. Among them, earthquakes of M≥7.5 have occurred on the NW and NE-trending faults with a greater strike-slip component in the fault tectonic zones.