Central Asia is rich in oil and gas resources and has great export potential. Strengthening energy cooperation with Central Asian countries can increase the coefficient of China’s energy security. In this paper, the Fergana basin in Central Asia is taken as the main research object. Through the analysis of structural deformation, it is found that the typical out- of- sequence thrust faults are developed in the margin of the Fergana basin. Combined with the sedimentary environment replacement of the basin, the tectonic evolution of the Fergana basin since the Mesozoic is reconstructed. The basement of Fergana basin was formed in the Late Paleozoic, which is related to the closure of the Southern Tianshan Ocean at the end of the Carboniferous. From Triassic to Jurassic period, Fergana basin entered the intracontinental depression stage and deposited a set of fluvial and lacustrine clastic rocks. Late Jurassic- early Cretaceous period, due to the closure of the Meso- Tethys, the Fergana basin turned into the compression stage. From Cretaceous to Paleogene, influenced by the expansion of the Neo- Tethys Ocean, a regional transgression event occurred in the south of the Tianshan Orogenic Belt. A large number of organisms developed, and high- quality source rocks were deposited in the basin. With the collision between the Arabian block and Eurasia continent across the Paleogene and Neogene transition, the Neo- Tethys Ocean finally closed, and the Fergana basin entered the compressional stage again. From Neogene to Quaternary period, a huge thickness of continental clastic deposit was deposited in the basin, and angular unconformity between Paleogene and Neogene was developed in the basin. Under the influence of continuous convergence between India and Eurasia continents, the Fergana basin began the foreland basin evolution stage during the Quaternary. Through the comparison of source- reservoir- cap rock assemblages and tectonic evolution of petroliferous basins in the northern and southern flanks of the South Tianshan Suture, it is found that the Upper Paleozoic of the Fergana basin has a good potential of oil and gas resources. Our research expands the prospects for oil and gas in the Fergana basin.