Abstract: Closely flying by asteroids can help to capture asteroid surface images, measure asteroid spectra, and obtain physical and chemical properties of asteroids. In particular, flying by multiple asteroids with potential hazards to the earth in one mission will significantly improve the understanding of the characteristics of potentially hazardous asteroids, and it is also of great significance to asteroid defense missions. In this paper, the trajectory of the multiple asteroid flyby mission of potentially hazardous asteroids was optimized. Firstly, the time and position distribution of asteroids passing through the ecliptic plane were analyzed, and the basic strategy of asteroids flyby in the ecliptic was determined. The time of asteroids crossing the ecliptic was taken as the time of asteroids’ flyby. Secondly, the sequential flyby sequence was optimized via beam selection tree search algorithm, and an optimization model for fast and effective solution of asteroid sequential flyby mission trajectory was established. Simulation results show that missions launched from 2024 to 2028 can fly by at least 18 potentially hazardous asteroids, especially the launch window in September 2027, which can fly by 21 potentially hazardous asteroids within a ten-year mission duration.