Cumulative fouling characteristics are often overlooked by researchers when optimising the operation of multi-effect distillation seawater desalination system. In order to analyse the influence of fouling cumulation on the optimisation operation, an eight-effect dynamic model for multi-effect distillation with thermal vapour compression (MED-TVC) seawater desalination system has been established and the cumulation of fouling has been considered in this model. Operation parameters of the eight-effect MED-TVC desalination system have been optimised repeatedly at different times (namely at different levels of fouling cumulation) throughout the full-cycle. Results indicate that the cumulation of fouling will gradually let the system deviate from the optimal operation condition, resulting in decrease in fresh water production, and operation re-optimisation at different times gets different results, which can efficiently reduce the influence of fouling and obtain better operational benefits. This work concludes that fouling cumulation has a big impact on operation optimisation of MED-TVC systems, and it is necessary to timely re-optimise operation parameters.