The selection of the most unfavorable axial force has a great influence on the seismic calculation results of bridges. The relevant bridge seismic specifications do not specify what is the “most unfavorable axial force”. The author compared and analyzed the ultimate bearing capacity of bridge piers under different axial forces and obtained the following results: (1) When checking the strength of bridge piers, the calculation results are quite different when three different internal force combinations are taken: the combination of constant load axial force and maximum bending moment, the combination of maximum bending moment corresponding axial force and maximum bending moment, and the combination of minimum axial force and corresponding bending moment; (2) When checking the shear strength of potential plastic hinges, the calculation results of using three different axial forces as the “most unfavorable axial force” are quite different when the constant load axial force, the axial force corresponding to the maximum bending moment, and the minimum axial force are taken; Through this study: (1) When calculating the maximum shear force of the bridge pier, the axial force corresponding to the maximum bending moment should be used as the “most unfavorable axial force” for calculation; (2) When checking the strength of bridge piers, the combination of the axial force corresponding to the maximum bending moment and the maximum bending moment should be used for calculation.