In practical application, it is very important to master the influence of structure parameters on the mid-span deflection quantificationally. For large-span and heavy-duty gantry cranes, the influence of the rigid leg and the soft leg on mid-span deflection has not been considered in the past. In the paper, the mathematical model is established for universal large-span and heavy-duty gantry cranes. The analytical solution for the mid-span deflection of gantry-frame structure girder is derived and obtained based on the variation principle by considering the coupling effect of the bending moments of girder and legs, the axial force and the secondary bending moments. The relation between the load and the deflection on the mid-span of the gantry-frame structure girder is known. Then, the experimental model is designed according to dimensional analysis method. And experiments were performed on the WEW-600B type testing machine. Hackling experimental data, the regular of the load and deflection on the girder mid-span is obtained, namely, the deformation of the gantry-frame structure resists the extal load to do work. The validity of the nonlinear analytical solution of the girder deflection is verified. Experimental results show that the analytical solution of the gantry-frame structure deflection has much higher calculation accuracy than previous calculation method. This work provides a theoretical basis for the design and inspection of gantry-frame structures.