The practice of oil and gas exploration shows that the palaeo-uplift in the basin plays an important role in the development and distribution of oil and gas fields. Based on the drilling data and seismic data, the genesis of the Indosinian palaeo-uplift in the Western Sichuan Depression was researched. It is shown that the western Sichuan region not only developed NE trending paleo-uplift in front of Longmen Mountain in the early Indosinian period, but also developed EW trending paleo-uplift in the Western Sichuan Depression. It is tentatively concluded that the closure of the Paleo-Tethys Ocean during the Indosinian period is the driving force for development of the paleo-uplift in Western Sichuan Depression. The formation of the NE trending paleo-uplift is related to the SE-NW trending thrust-nappe compression of the Jiangnan-Xuefengshan paleo-uplift belt, and the formation of EW trending paleo-uplift is related to the SN trending strong compression of the Yangtz Plate and the North China Plate along the Mianlue suture belt.