In high-voltage cables, because of the close fit of their internal structures, interface pressure is generated between conductor and insulator, which affects the performance of the cable. Studies on the calculation and testing of the interfacial pressure of cable conductors are scarce because of the lack of a unified formula and the difficulty of direct measurement. As such, in this study, we devised two methods for calculating and measuring the interface pressure of cable conductors. In the first, we used two physical experimental methods. We used the friction between cable components to perform the calculation and create an experimental method for determining cable conductor interface pressure; on the basis of the equation of the pressure inside and outside a thick-walled cylinder using elasticity mechanics, we calculated the interface pressure on the basis of the measurement of the strain state of the inner and outer diameters of each layer of the cable under different assembly and stripping conditions. We verified the effectiveness of the methods through physical tests and simulations using a YJLW03 1 × 1200 high-voltage cable. Then, we used simulation software ANSYS and SolidWorks to calculate the interface pressure. With different simulation settings, we obtained results regarding interface pressure. Lastly, these simulated values were individually compared with two physical tests, and the error was calculated. Results obtained in the ANSYS environment showed that interface pressure values determined by the geometric interference normal stress, geometric interference pressure, contact interference normal stress, and contact interference pressure methods were 39.75, 36.84, 5.76, and 36.57 MPa, respectively. In SolidWorks software, we used the contact-stress and X-axis normal stress methods. Results were all 37.36 MPa. Then, simulation results and experimental results were compared, and error was calculated. The comparison showed that the X-axis orthogonal stress method was the most accurate. Errors between the X-axis orthogonal stress method and the two physical experiments were 1.5% and 0.48%. Through the above simulation and physical experiments, we determined the interface pressure between conductors and insulators in a high-voltage power cable. We obtained the cable interface pressure value through two kinds of physical experiments, and these two methods were clearly reliable. Simulation experiments showed that using SolidWorks software to simulate this problem obtained better results. Research results provide technical support and reference for the calculation and measurement of cable interface pressure and the optimization of cable performance.