The route planning is an important part of UAV mission planning, especially for anti-submarine ship-based UAV. When a ship-based UAV searches submarine, it must be planned a route reasonable. Various restricted conditions are considered in this paper, including the capability, oil cost, air threat, and aviatic area. Under the condition of reasonable assumed tactics, an optimal route, which is from the original point to the target point, is planned for the ship-based UAV, with voronoi diagram, Dijkstra algorithm, and genetic algorithm. The method and the result provide an efficacious guarantee for the ship-based UAV to complete the mission of searching submarine