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The influence of irradiation should be considered in fatigue reliability analyses of reactor structures under irradiation conditions. In this study, the effects of irradiation hardening and irradiation embrittlement on fatigue performance parameters were quantified and a fatigue life prediction model was developed. Based on this model, which takes into account the cumulative effect of a neutron dose, the total fatigue damage was calculated according to Miner’s linear cumulative damage law, and the reliability analysis was carried out using the Monte Carlo simulation method. The case results show that the fatigue life acquired by taking into account the cumulative effect of irradiation was reduced by 24.3% compared with that acquired without considering the irradiation effect. Irradiation led to the increase of the fatigue life at low strains and its decrease at high strains, which is in accordance with the findings of an irradiation fatigue test. The rate of increase in the fatigue life decreased gradually with the increase of the neutron dose. The irradiation performance parameters had a small influence on fatigue reliability, while the fatigue strength coefficient and the elastic modulus had a great influence on the fatigue reliability. Compared with the current method, which uses a high safety factor to determine design parameters, a fatigue reliability analysis method taking into account the cumulative effect of irradiation could be more accurate in the reliability analysis and life prediction of reactor structures