Void closure in large ingot during hot forging is a multiscale problem. Based on the cell model and the theory of mesomechanics, the evolution equation of void volume is derived. By analysis of mechanics condition of void closure, the Z-C criterion of void closure for large-ingot hot forging is established. The Z-C criterion explains quantitatively almost all of the best findings of void closure for large-ingot hot forging and rolling processes. In addition, new and significant effects of the hardening exponent, the remote stress triaxiality and the equivalent strain on void closure, which have not been found in previous researches, are revealed. By comparing the traditional method with the application of the Z-C criterion of void closure, it is clear that the Z-C criterion provides a novel way for process design and optimization in terms of elimination of voids in large ingots.