Aiming at the problem that the overall rigidity of pre-stressed unitized frame was directly affected by the bias load working condition, which indirectly affected the forming quality of workpiece, therefore, based on the pre-stressed unitized frame numerical model of a certain heavy isothermal forging hydraulic press, three typical working conditions of central loading, extreme bias load in x-direction and extreme bias load in y-direction were calculated by finite element software ABAQUS, and the design rationality of the overall structural design of the frame was verified from the perspectives of stiffness and strength. Then, the overall stiffness of the pre-stressed unitized frame under different bias load working conditions was focused on discussing, and by extracting a series of typical key points on the column as the characteristic edges, the curves for the detailed displacement and equivalent stress results were plotted, then a comparative analysis was conducted to obtain the data trend and difference values intuitively,which reveales the influence laws of different bias load working conditions on the column displacement, equivalent stress distributions and frame opening trend were quantitatively.