In order to understand the performance of a large-capacity VTE-MED nuclear seawater desalination systemthoroughly, the responding characteristics of the system to the off-design operating conditions were studied. Theinfluence of scale deposit in tubes on the heat transfer areas needed and on the heat transfer coefficients with high topboiling temperature (TBT) was illustrated. The decrease of GOR, and also the damage to the normal operation of thesystem caused by temperature drop of feed brine because of seasonal variation, were explored, based on which acorresponding approach for adjusting feed brine flow rate was proposed. An optimal brine feed flow rate was alsoproposed to obtain the highest GOR under different heat loadings. The work could be helpful for the efficient and safeoperation of nuclear VTE-MED desalination plants.