PURPOSE: COVID-19 is a new infectious disease with global spread. The aim of the present study was to explore possible risk factors and evaluate prognosis in COVID-19 with liver injury. METHODS: A retrospective study was conducted on 356 COVID-19 patients in the Third People's Hospital of Yichang, Hubei, China. Clinical characteristics and laboratory tests between patients with and without liver injury were compared, while risk factors of COVID-19-related liver injury were analyzed. Univariate and multivariate Cox regression analyses were conducted to identify risk factors of in-hospital death. RESULTS: Of the patients with liver injury, severe and critical types of COVID-19 comprised 12.43% and 14.69%, respectively, higher than in patients without liver injury (both P<0.05). CRP and male sex were independent risk factors for for patients with liver injury, while decreased lymphocyte count (HR 0.024, 95% CI 0.001-0.821) and elevated monocytes (HR 1.951, 95% CI 1.040-3.662) and CRP (HR 1.028, 95% CI 1.010-1.045) were independent risk factors of prognosis of death in COVID-19 patients with liver injury. CONCLUSION: Liver injury is a common complication in severe COVID-19 patients. Male sex and elevated CRP were independent risk factors in COVID-19 complicated by liver damage. Liver damage with increased CRP and monocyte count and decreased lymphocyte count may imply a poor prognosis.