Abstract A three-dimensional integrated circuit (3D-IC) is representative of technologies that have achieved the “beyond Moore's Law” concept. However, a 3D-IC suffers from the thornier problems of local overheating and thermal stress concentration as a result of its higher integration. Herein, a 3D-IC model with a real microprocessor structure to explore the temperature and thermal stress distributions under a closed microchannel liquid cooling condition. Finally, the effects of the structural parameters, flow direction of the cooling water, and core area overclocking on the maximum temperature, thermal stress distribution, and total pressure drop inside the 3D-IC model were investigated. The numerical results indicated that a mixed arrangement of micro-pin fins in the bottom microchannel and in-line arrangement in the upper microchannel was beneficial for balancing the maximum temperature and pressure drop. Moreover, the maximum thermal stress decreased by 34% after parallel flow and an optimized upper microchannel structure were adopted in the 3D-IC. Furthermore, the reliability of the chip with the optimized structure was governed by the thermal failure risk instead of thermal stress. Therefore, to balance the reliability and pumping power consumption of chips, maintaining the maximum temperature at 333 K could be a reference for 3D-IC coupling management.