The high incidence of liver injury in patients with COVID-19 and the need for long-term medication for recovery make it imperative to study the infectivity and pathogenicity of SARS-CoV-2 in the liver. Here, we have identified significant proteomic changes for the first time in the liver of patients with COVID-19 using a quantitative proteomics approach. We detected differential expression levels of several proteins that mediate characteristic cellular host responses elicited by SARS-CoV-2 infection. These findings reveal important molecular mechanisms that may play a key role in the pathogenesis of COVID-19 associated liver diseases and provide a scientific basis for medical intervention strategy and drug target selection.