Horizontal press as an important part of hydro-forming machine is used to output the horizontal force to keep the high internal pressure during tube hydro-forming. However, the horizontal press frame is usually mounted on the press bed and not pre-stressed. Meanwhile it will be subjected to the reaction force caused by liquid pressure. Stresses are concentrated severely on the assemble region due to deformation, and total fatigue life will decrease. In order to predict the total fatigue life of the frame, the simulations are used firstly to determine to stress concentration region, and then strain gauge measurements are carried out under different loads. Next, the methods of statistical probability are conducted to calculate the fatigue life based on long-term load history. Finally a structure with the considerable longer fatigue life is redesigned.