Based on dean-flow-coupled elasto-inertial effects, 3D particle focusing in a straight channel with asymmetrical expansion–contraction cavity arrays (ECCA channel) is achieved. First, the mechanism of particle focusing in both Newtonian and non-Newtonian fluids was introduced. Then particle focusing was demonstrated experimentally in this channel with Newtonian and non-Newtonian fluids using three different sized particles (3.2μm, 4.8 μm, 13 μm), respectively. The influences of flow rates on focusing performance in ECCA channel were studied. Results show that in ECCA channel particles are focused on the cavity side in Newtonian fluid due to the synthesis effects of inertial and dean-drag force, whereas on the opposite cavity side in non-Newtonian fluid due to the addition of viscoelastic force. Compared with the focusing performance in Newtonian fluid, the particles are more easily and better focused in non- Newtonian fluid. A further advantage is three-dimensional (3D) particle focusing in non-Newtonian fluid is realized according to the lateral side view of the channel while only two-dimensional (2D) particle focusing can be achieved in Newtonian fluid. Conclusively, this Dean-flow-coupled elasto-inertial microfluidic device could offer a continuous, sheathless, and high throughput (>10000 s-1) 3D focusing performance, which may be valuable in various applications from high speed flow cytometry to cell counting, sorting, and analysis.