Aiming at the water takeoff safety of vertical take-off and landing Unmanned aerial vehicle (UAV) on water in complex sea conditions, a numerical simulation method for wave takeoff safety of UAV based on Computational Fluid Dynamics (CFD) technology is proposed, which is based on overlapping mesh technology and Dynamic Fluid Body Interaction (DFBI) model to solve the solid motion response, Volume of Fluid (VOF) model to simulate the gas-liquid multiphase flow, K-Epsilon model to simulate the turbulent flow. And the takeoff power is simulated by coupling the upper custom force instead of propeller pull in the DFBI model. The results show that when the water UAV is located in the trough-waist-peak zone of the wave for takeoff, it can successfully fly away from the water, especially in the trough-waist zone, which is the most suitable for takeoff. When the water UAV is located in the peak-waist-valley zone for takeoff, it is prone to capsize or propeller hitting the water and cannot take off safely.