Fault sealing evolution is analyzed based on normal stress calculation, and combined with migration pathway pattern division, and favorable areas of fault-lithologic reservoirs of Dainan Formation are predicted in Gaoyou Depression. It is concluded that the critical value of fault sealing is 13.8 MPa. Most of the reservoir faults are open in the accumulation period and closed now. However, there is one reservoir fault sealing all the time, which is Shaoshen 1 reservoir of own source type. East Lian 12 oil-west Yong 22 oil and east Shao 14 oil are the most favorable areas of fault-lithologic reservoirs of Dainan Formation in Gaoyou Depression. Deep Shaobo sub-sag to the northwest of Shaoshen 1 reservoir is the secondary favorable area.