Abstract: Taking the steam generator of Daya Bay Nuclear Power Plant as the prototype, the simplified physical model of steam generator was established based on the similarity principle. The vapor-liquid two-phase flow boiling phase change process and thermal stress variation were simulated by two-fluid model and the basic thermal elasticity mechanics formula respectively. The flowing heat transfer on both the primary and the secondary sides and the coupled heat transfer between fluid and heat transfer tubes were numerically simulated using CFX software. The temperature load of fluid was transferred to the tubes in ANSYS WORKBENCH, and then steady-state thermal analysis and thermal stress analysis were carried out. The simulation results show that the steam quality at outlet of the secondary side is 24.5% and the temperature of coolant at outlet is 296.2 ℃, which are in good agreement with the actual operating parameters of steam generator in Daya Bay Nuclear Power Plant. The distribution of the thermal stress is consistent with that of temperature difference of the tube’s wall. In addition, thermal stress along the wall thickness direction decreases and then increases, and neutral layer exists in the tube. The maximum thermal stress of the tube is 54.5 MPa. These results can provide theoretical support to the optimization of the design and safe operation in steam generator.