A structural optimization study of the downhole oil-water separator that consists of two series de-oiling hydrocyclones has been performed. The particle swarm optimization algorithm combined with Plackett-Burman Design, steepest ascent design and response surface methodology has been used in the optimization. The optimized geometry has a better separation performance for the oil droplets whose particle sizes are smaller than 35.78 µm. The laboratory experiment validates that the proposed method can improve the separation performance of the downhole oil-water separator.