[Objective] The response of landscape ecological risk to the change of land use pattern was explored in order to provide scientific support for promoting the sustainable use of land resources and maintaining regional ecological security. [Methods] Based on the evolution of land use in Guangzhou City from 2001 to 2017, the future land use simulation (FLUS) model was used to simulate the spatial distribution of land use under the natural development scenario and the “three-line” (ecological protection red lines, permanent basic farmland protection red lines, urban development boundary lines) constraint scenario in 2025. Then the landscape ecological risk assessment model was constructed to analyze the situation of landscape ecological risk and its spatial-temporal response to land use change in Guangzhou City. [Results] From 2001 to 2017, the area of construction land continued to increase, while the area of other land types continued to decrease. The change range of grassland, construction land and unused land was larger. Compared with 2017, the construction land was expected to expand significantly under the natural development scenario of Guangzhou City in 2025. The expansion of construction land would be restricted under the “three lines” constraint scenario, the reduction of land area such as forest land and water area was expected to decrease, while the cultivated land was expected to increase slightly. From 2001 to 2017, the landscape ecological risk index of Guangzhou City increased continuously. The spatial distribution of risk levels showed a circle layered structure with high center and low surrounding. The scale of low and lower ecological risk areas was reduced, while the scale of high and higher ecological risk areas was increased gradually. [Conclusion] Compared with 2017, the landscape ecological risk index under the two scenarios will increase in 2025, while the ecological risk index under the “three-line” constraint scenario has a smaller increase, which is more in line with the needs of future urban construction and ecological protection of Guangzhou City.