Under the action of electrothermal–mechanical coupling, the failure and performance degradation of electronic devices are prone to occur, which has become a significant reliability problem in micro-electronic packaging. The improvement of flip chip reliability by using thermal interface materials was studied. First, a three-dimensional finite element model of the flip chip packaging system and the finite element simulation of electric-thermal-force multifield coupling were conducted. Then, the Joule heating, temperature distribution, thermal stress, and deformation of the flip chip under high current density were analyzed. At the same time, the influence of thermal interface material's thermal conductivity and operating current on flip chip reliability was studied. The result showed that when the thermal interface material (TIM) thermal conductivity increased from 0.2 W/m·K to 6 W/m·K, the maximum temperature and maximum equivalent stress in the flip chip were reduced by 6.35 °C and 14.6 MPa. Then, the reliability experiment of the flip chip connected to the radiator under high current density was performed, and the temperature change in the flip chip under different thermal interface materials was obtained. Finally, through the combination of experiment and simulation, the influence of thermal interface materials on flip chip reliability was analyzed. The result showed that when the thermal interface material's thermal conductivity was 0.2 W/m·K, 3 W/m·K, 6 W/m·K, the corresponding temperature in the flip chip system was 111.2 °C, 105.0 °C, 102.7 °C. It is further confirmed that electronic devices' reliability and service life were effectively improved using the high thermal conductivity boron nitride nanosheets/epoxy composite material prepared in this paper.