In this paper, the generalized hydrodynamic force and response of a flexible body are calculated at different reference coordinate systems. We generalize the equation of motion for a flexible body by using the conservation of momentum (Mei et al., 2005). To obtain the equations in the generalized mode, two different reference coordinates are adopted. The first is the body-fixed coordinate system by a rigid body motion. The other is the inertial coordinate system which has been adopted for the analysis. Using the perturbation scheme in the weakly-nonlinear assumption, the equations of motion are expanded up to second-order quantities and several second-order forces are obtained. Numerical tests are conducted for the flexible barge model in head waves and the vertical bending is only considered in the hydroelastic responses. The results show that the linear response does not have the difference between the two formulations. On the other hand, second-order quantities have different values for which the rigid body motion is relatively large. However, the total summation of second-order quantities has not shown a large difference at each reference coordinate system.