This study provides an integrated interpretation for the Mesozoic - Cenozoic tectonothermal evolutionary history of the Permian strata in the Qishan area of the southwestern Weibei Uplift, Ordos Basin. Apatite fission-track and apatite/zircon (U-Th)/He thermochronometry, bitumen reflectance, thermal conductivity of rocks, paleotemperature recovery, and basin modeling were used to restore the Meso-Cenozoic tectonothermal history of the Permian Strata. The Triassic AFT data have a pooled age of ~180±7 Ma with one age peak and P(χ2)=86%. The average value of corrected apatite (U-Th)/He age of two Permian sandstones is ~168±4 Ma and a zircon (U-Th)/He age from the Cambrian strata is ~231±14 Ma. Bitumen reflectance and maximum paleotemperature of two Ordovician mudstones are 1.81%, 1.57% and ~210°C, ~196°C respectively. After undergoing a rapid subsidence and increasing temperature in Triassic influenced by intrusive rocks in some areas, the Permian strata experienced four cooling-uplift stages after the time when the maximum paleotemperature reached in late Jurassic: (1) A cooling stage (~163 Ma to ~140 Ma) with temperatures ranging from ~132°C to ~53°C and a cooling rate of ~3°C/Ma, an erosion thickness of ~1900 m and an uplift rate of ~82 m/Ma; (2) A cooling stage (~140 Ma to ~52 Ma) with temperatures ranging from ~53°C to ~47°C and a cooling rate less than ~0.1°C /Ma, an erosion thickness of ~300 m and an uplift rate of ~3 m/Ma; (3) (~52 Ma to ~8 Ma) with ~47°C to ~43°C and ~0.1°C /Ma, an erosion thickness of ~500 m and an uplift rate of ~11 m/Ma; (3) (~8 Ma to present ) with ~43°C to ~20°C and ~3°C/Ma, an erosion thickness of ~650 m and an uplift rate of ~81 m/Ma. The tectonothermal evolutionary history of the Qishan area in Triassic was influenced by the interaction of the Qinling Orogeny and the Weibei Uplift, and the south Qishan area had the earliest uplift-cooling time compared to other parts within the Weibei Uplift. The early Eocene at ~52 Ma and the late Miocene at ~8 Ma, as two significant turning points after which both the rate of uplift and the rate of temperature changed rapidly, were two key time for the uplift-cooling history of the Permian strata in the Qishan area of the southwestern Weibei Uplift, Ordos Basin.