At present, the preheating temperature rise rate of the Residual Heat Removal system (RRA) of the M310 and CPR1000 units is controlled below 60 °C/h. In order to shorten the critical path time of overhaul, it is planned to increase the preheating temperature rise rate to no more than 120 °C/h. There is a large uneven temperature distribution in the axial and radial directions of the RRA heat exchanger tube sheets, which may lead to large thermal strain and thermal stress. When the thermal stress range is large enough, thermal fatigue damage is very likely to occur. In this paper, according to an improved full-life fatigue analysis and evaluation method, the conjugate calculation model of the RRA heat exchanger tube sheets is established, the mechanical stress and thermal stress of the RRA heat exchanger tube sheets under various operating conditions is calculated and analyzed, and the full-life fatigue performance analysis is performed under various combined loads. The analysis and evaluation results show that under various operating conditions, the cumulative use factor of the RRA heat exchanger tube sheets is 0.737, which meets the fatigue acceptance criterion of the cumulative use factor less than 1.0. Therefore, there is no fatigue risk of the RRA heat exchanger tube sheets during the entire life.