Residual oil saturation variations exists in marine sandstone oil fields under long-term water flooding, which limits the accuracy of reservoir numerical simulation historical matching and residual oil recognition. So, it is necessary to carry out research and application of the relative permeability time-dependent characterization and simulation method. Physical simulation and saturation benchmarking of crossing wells are used to quantitatively characterize the residual oil saturation endpoint in long-term water flooding and establish a series of time-dependent relative permeability group. By improving traditional numerical simulation software, the calling function of water-drive multiples field is increased and embedded into history full-process iterative algorithm, and finally realize the historical matching considering the relative permeability time-dependent. The application in Nanhai X oilfield shows that the residual oil saturation has a logarithmic relationship with water-drive multiples in long-term water flooding. The accuracy of saturation along crossing well and production dynamics matching is considerably improved with time-dependent simulation.The ‘Matthew Effect’ of remaining oil distribution is obvious. Guided by the study, the adjustment wells have better potential tapping performance and well fit the model, which provides technical reference for the study and oil recovery enhancement at late development stage.