Abstract: For sealing reliability problem with quick-opening clamping and horizontal deep-sea simulated cabin,this paper presents an O-ring radial sealing structure of deep-sea simulated cabin,and establishes a nonlinear finite element model for the structure. Its sealing reliability through O-ring's sealing contacted stress and Von Mises stress were evaluated,and the effect of medium pressure,O-ring's pre-compression ratio,and groove chamfering and clearance on the sealing performance were analyzed. Simulation results show that contacted stress peak area significantly changes with increasing pressure,O-ring and Von Mises stress distribution dramatically changes when the pressure increases from 0 MPa to 25 MPa,however,they do not almost change when the pressure increases from 25 MPa to 45 MPa. The main sealing width will raise with increasing pre-compression ratio,and groove chamfer increasing is helpful for Von Mises stress reduction. Von Mises stress peak value first increases and then decreases with increasing clearance,and the increase of clearance is helpful to improve the sealing width. Experiment results show that when the O-ring pre-compression ratio is 10%,the groove chamfer is 0. 4 mm,clearance is 0. 7 mm,and the sealing structure can ensure high sealing reliability under 40,45 and 50 MPa.