To address the issue of strong empirical nature in gradation formulation during the mix proportion design of hot mix asphalt (HMA), through mathematical derivation, laboratory tests, and statistical analysis,an analytical expression of the interference coefficient of fine aggregates was established, the interference coefficients of fine aggregates for each gradation of three commonly used HMA mixtures (AC-13, AC-20 and AC-25) were calculated, an estimation model for the voids in mineral aggregate without asphalt (VMAa) of HMA was constructed, and a HMA gradation optimization design method was proposed. The results show that overall from AC-13, AC-20 to AC-25, the interference coefficient decreases progressively, and the statistical model between the interference coefficient and the weighted average particle size of coarse aggregates is effective; the VMAa estimation model is simple and practical, can quickly predict the relative magnitude of VMAa for different gradation curves, and achieves gradation optimization design.