The Future Land Use Simulation (FLUS) model is a new model for simulating multiple land-use changes, and has a broad application prospect. This paper improved the FLUS model by incorporating a spatial autocorrelation factor into the Artificial Neural Network (ANN) module of FLUS, selected thePearl River Delta region as the case study area, and validated the improved FLUS model based on the land use data of 2009 and 2015, as well as a series of driving factors. Three future land-use scenarios in 2035: the baseline scenario, cultivated protection scenario, and ecological protection scenario, were simulated using the improved model. The results showed that: (1) After incorporating the spatial autocorrelation factor, the model had better predictive powerfor the occurrence probability distribution ofeach land use. The ROC values of cultivated land, forestland, water area,construction land, and unused land increased from 0.819, 0.928, 0.885, 0.855, and 0.861 to 0.857, 0.934, 0.890, 0.863 and 0.978, respectively. (2) The simulation accuracy of the improved FLUS model was improved. The Kappa value increased from 0.732 to 0.744, and the FOM value increased from 0.077 to 0.106. (3) The scenario simulation results indicated that under all three scenarios, forestland and construction land would increase, whereas cultivated land would decrease. Apparent differences also existed in the simulated change sizes and locations of each land use type under different scenarios. Under the baseline scenario, construction land would expand rapidly at the expense of a large amount of cultivated land. Under the cultivated land protection scenario, cultivated land area would remain at a reasonable level, the expansion of construction land would alleviate, and the land use layout would tend to be reasonable. Under the ecological protection scenario, cultivated land, forestland, and water area would be well protected, the layout of construction land would be more rational, and the land use sustainability in the study area would be improved significantly.