In order to solve the problem of low safety of unmanned aerial vehicles ( UAVs ) operating in complex low-altitude environment, a route planning method for UAVs with regional risk assessment was proposed, and it could quickly generate a route with low operational risk. Firstly, the complex low-altitude environment was simplified by model and risk assessment, and the low-altitude three-dimensional risk map was obtained. Taking the path risk value as the comprehensive cost, the improved ant colony algorithm was used to plan the three-dimensional space path, it effectively reduced the redundancy of the generated path. Finally, cubic B-spline is used to smooth the planned discrete path and generate a continuous flightable path with curvature and pitch angle. The simulation and experimental results show that the generated path can be exchanged for a path with a lower risk value at a lower path cost, and at the same time, the path redundancy is low, and the curvature and pitch Angle continuously change, so it is a flight-able path that meets the performance constraints of UAV.