Nanoporous gold (np-Au) is a kind of metallic foam that has nanoscale ligaments and pores. Based on its high specific surface area and chemical stability, it has been widely applied as a functional material in sensors, actuators, catalysis, and the like. According to previous research, in contrast to solid gold, np-Au shows catastrophic brittle fracture after elastic deformation rather than plastic behavior. Assessing the mechanical characteristics of np-Au is critical in estimating its structural reliability. In this study, we looked for the origin of the indentation size effect (ISE) in nanoporous gold and its dependence on ligament size in two different fracture modes: collapse and shearing beneath an indenter. We derived a theoretical ISE model as an inverse function of indentation depth. To verify the model, uniaxial compression and shear tests were performed on four np-Au samples of different ligament sizes. The model appropriately estimated a decrease in indentation hardness of np-Au with indentation depth. We found ligament-size-dependent ISE in np-Au by normalizing hardness and indentation depth, which can be explained by different size effects in compressive and shear deformation of np-Au, and by dislocation movement in ligaments junctions of each sample, resulting in strain-hardening by dislocation pileup.