Tectono-thermal history is not only important to understand basin evolution and its geodynamic mechanism, but also the key question to be solved for source rock maturation study. With the increasing energy demand and difficulty in oil and gas discovery on land, sea basin has gradually become an important replacement area for oil and gas exploration and a hotspot of the national energy strategy research. Qinnan Depression is on northwest of the Bohai Sea area, with good exploration prospects but low exploration degree. In this study, 25 artificial wells have been established based on 3 seismic profiles in the Qinnan Depression, and then their tectonic subsidence history and thermal history has been modeled to reconstruct the tectonic-thermal evolution history of this depression. The results indicate that since the Cenozoic era, the Qinnan Depression has undergone three stages of rifting and stretching during the sedimentary periods of the Kongdian Formation to fourth member of the Shahejie Formation (65-42 Ma), the third member of the Shahejie Formation (42-38 Ma), and the third member of the Dongying Formation (32.8-30.3 Ma), with a total stretching factor of 1.27~2.05. Corresponding to the three stages of stretching, the basal heat flow of the Qinnan Depression has experienced three stages of increase, reaching a peak of 64.0~89.0 mW/m² at the end of the deposition of the third member of the Dongying Formation (~30.3 Ma), and then decreased gradually until present. There is a good coupling relationship between the tectonic-thermal evolution process and fault activity in the Qinnan Depression, and multiple stages of heating are conducive to the mature and hydrocarbon generation of its source rocks.