For APE400 closed double-point integral frame press, the topology-geometry parameter optimization study of the frame structure for manufacturing was carried out,aiming at the critical load-bearing frame base and column with large mass proportion. Then, the static mechanical properties of the original press frame structure were analyzed, and the influences of the two connection methods of fixed lower die and base and sliding friction contact on its deformation were conformed. Because the table surface deformation of latter was larger than that of former, the frame structure verified by sliding friction contact simulation was more conservative and closer to the reality. Furthermore, the material topology composition of the base supporting the die and the side columns of frame was obtained respectively by a variable density topology optimization method, and the parametric model of the new frame structure was established according to the actual plate welding manufacturing process. Finally, the geometric parameter optimization was conducted by the response surface optimization method, and the performance indexes of the optimized model and the original model were compared. The results show that the weight reduction of 3130 kg can be achieved when the deformation difference of the upper table surface for the die is 0.19 mm, and the weight reduction of 3803 kg can be achieved when the deformation difference is 0.26 mm which is the same as that of the original model, and the weight reduction ratio reaches 18.46%, which is a remarkable effect for the structural lightweight.