Abstract: In order to investigate the material removal mechanism, technological rules, and optimization of technological parameters, experimental investigations of laser drilling on polystyrene(PS) with single-pulse and multi-pulse nanosecond solid-state laser at 266 nm based on the single factor experiment and orthogonal experiment method were carried out. The material removal mechanism was analyzed, and the relationship between the diameter and depth of the micropore and the number of laser pulses, the laser pulse energy and the defocusing distance was obtained. As well as an optimized combination of process parameters meeting the requirements was acquired. The experimental results show that when the laser pulse energy is 0.110 mJ, the micropore with regular shape, better roundness, and smaller recast layer was obtained; when the laser pulse energy is 0.500 mJ, the shape and roundness of micropore becomes worse, and the width of recast layer becomes larger at the same time. During the multi-pulse drilling, no recast layer is present at the entrance of the through-hole with the laser pulse energy of 0.040 mJ, and the removal mechanism is mainly photochemical. With the laser pulse energy of 0.390 mJ, the recast layer is more visible at the entrance of the through-hole and over-ablation occurs at the entrance edge, the removal mechanism is mainly photothermal. Laser pulse energy and defocusing distance have a large effect on the hole diameter, and the number of laser pulses and positive defocusing distance have a large effect on the hole depth. The optimized combination of parameters obtained from the orthogonal experiments that micropores of good quality can be produced when the number of laser pulses is 50, laser pulse energy is 0.021 mJ and defocusing distance is 0 μm. This investigation provides a reference for 266 nm nanosecond laser processing of polystyrene target.