This paper proposes a laser self-mixing interference (SMI) detection method that simple structure, easy collimation, and can detect single micro-nano particle. A laser SMI signal model generated by a single particle is established, the characteristics of the interference signal are theoretically analyzed, and a microfluidic particle detection system is built. Self-developed LabVIEW program is used to carry out detection experiment and signal acquisition of polystyrene particles, and the diameter of a single particle is analyzed from both the time-domain and frequency-domain. The results show that the method can effectively detect and distinguish polystyrene microspheres with diameters ranging from 0.5--10 μm.