The Cenozoic uplift and deformation process of the West Kunlun Mountains has an important impact on many aspects, including the geomorphology and hydrography evolutions, the distribution of mineral deposit and hydrocarbon reservoir, and the climate and environment change in Central Asia. However, there still lack a common understanding. The timing of the initial uplift and deformation in the Cenozoic West Kunlun Mountains were proposed to be the Paleocene, the Middle—Late Eocene and the late Oligocene—early Miocene, respectively. This article summarizes the studies of stratigraphy, sedimentology, provenance analysis and thermochronology in the Southwestern Depression in Tarim Basin, and discusses the timing, evidence, explanation and controversy of the Paleocene and Middle—Late Eocene uplift and deformation of the West Kunlun Mountains. On this basis, we determined that the West Kunlun was uplifted in the Paleocene and proposed the Middle—Late Eocene was an accelerated node in the Cenozoic deformation process. These two uplifts and deformations correspond to the remote response of the initial collision of the Indian—Asian continent and the slab breakoff of the Neo-Tethyan subduction respectively, which reflects the process of India—Asia collision and continuous compression of the Indian plate to the north.