The microwave load water-cooling system was operated in a vacuum cold black environment, and the pressure difference between the inside and outside of the water pipe could reach 0.3 to 0.4 MPa. To ensure the tightness of the water pipe, a conical seal structure was selected, the macro-static model and micro-boundary element contact model were established for the two forms with and without the Viton seal. The macro model simulation was performed by the finite element method to obtain the stress distribution inside the conical structure under different preload stress, the relationship between the contact pressure of the conical sealing interface and the contact area of the O-ring sealing interface as a function of preload stress; the method was used to calculate the micro-contact model, and the critical contact pressure and contact area to achieve the sealing requirements were obtained respectively without Viton seal and with Viton seal. As a result, a conical seal structure with a Viton seal was finally chosen for application. After verification, the structure meets the requirements for the use of microwave load water-cooling systems during the vacuum thermal test.