The work aims to study the effect of thickness ratio of different parts of the bottle on the top load of HDPE bottle aiming at the problem that a blow-molded milk HDPE bottle is easy to collapse, and carry out lightweight design to HDPE bottle. The physical 3D model of HDPE bottle was obtained by 3D scanning and the thickness of the bottle was measured. The finite element model of HDPE bottle shell with different wall thickness was built in ABAQUS, and the accuracy of the finite element model was verified by static pressure test. The effect of thickness ratio on the top load capacity of the whole bottle was simulated and analyzed, and the distribution of HDPE bottle materials was topologically optimized. When the top was loaded, the errors of the critical load and critical displacement obtained by finite element model simulation analysis and experiment were 2.49% and 5.11%, respectively. Combined with the optimization of thickness ratio and lightweight analysis, the amount of HDPE bottle material was reduced by 12 g. The finite element model of HDPE bottle considering the actual thickness of the bottle has high accuracy. For design of HDPE bottle, attention should be paid to the thickness composition of each part of the bottle, so as to obtain better mechanical properties.