A mineralization zone exists in the Middle and Lower Yangtze River (MLYR) region. Previous studies have shown that this zone might be caused by the rich ejection of magma in the Mesozoic. We have applied the teleseismic tomography method to determine a 3-D P-wave velocity structure of the mantle down to 500km depth beneath this region by using 14,740 P-wave arrival times collected from 519 teleseismic events recorded by 46 portable and 47 static seismic stations located in this region. The relative residual times used for the tomography are calculated by the modified multi-channel cross-correlation method which increases not only the efficiency but also the data precisions up to 0.01s. The grid space is set as 1°×1° horizontally and 50–100km vertically. Our tomographic results show that the lithosphere with high velocity anomalies is separated into two parts: one locates above the depth of 100km and the other at the depths between 250km and 400km, and the asthenosphere with low velocity anomalies locates between these two parts of lithosphere, which indicates that the lithosphere delaminated together with the asthenosphere upwelling. The detachment of lithosphere might relate to the subduction of the western Pacific slab. Therefore, our study provides clear evidence to geoscientists for understanding the deep dynamic process beneath this region and a three-stage geodynamic process is developed based on the new evidence. •The Middle-Lower Yangtze River is an important mineralization zone in China.•A 3-D velocity model down to 500 km deep is inverted by the teleseismic tomography.•The detachment of lithosphere and the upwelling of asthenosphere are clearly shown.•The three-stage geodynamic process is developed according to our results.