Crimean-Congo hemorrhagic fever virus (CCHFV) is a member of the family Nairoviridae in the Hareavirales order and is an important human pathogen. Hepatic injury is a salient feature of CCHF human disease and can be recapitulated in murine models. Here, we described techniques to study liver damage caused by CCHFV in the mouse system. These techniques include a description of the mouse model used to study disease, and classical histopathological methods. Additionally, the use of in situ hybridization to evaluate liver injury is described in the context of viral infection. Immunofluorescence staining techniques to identify infected and/or damaged Kupffer cells is also explained. This work provides a primer for the comprehensive pathophysiological study of liver infection by a virus, but also has utility for noninfectious liver injury as well.