In this paper a novel method for reliability prediction and validation of nuclear power units in service is proposed. The equivalent availability factor is used to measure the reliability, and the equivalent availability factor deducting planed outage hours from period hours and maintenance factor are used for the measurement of inherent reliability. By statistical analysis of historical reliability data, the statistical maintenance factor and the undetermined parameter in its numerical model can be determined. The numerical model based on the maintenance factor predicts the equivalent availability factor deducting planed outage hours from period hours, and the planed outage factor can be obtained by using the planned maintenance days. Using these factors, the equivalent availability factor of nuclear power units in the following 3 years can be obtained. Besides, the equivalent availability factor can be predicted by using the historical statistics of planed outage factor and the predicted equivalent availability factor deducting planed outage hours from period hours. The accuracy of the reliability prediction can be evaluated according to the comparison between the predicted and statistical equivalent availability factors. Furthermore, the reliability prediction method is validated using the nuclear power units in North American Electric Reliability Council (NERC) and China. It is found that the relative errors of the predicted equivalent availability factors for nuclear power units of NERC and China are in the range of –2.16% to 5.23% and –2.15% to 3.71%, respectively. The method proposed can effectively predict the reliability index in the following 3 years, thus providing effective reliability management and maintenance optimization methods for nuclear power units.