Objective: To investigate the clinical features of patients with liver failure caused by tumor diffuse liver infiltration. Methods: A retrospective analysis was performed for the clinical data of 1008 patients with liver failure who were admitted to our hospital from July 2009 to December 2015. Among these patients, 9 had acute liver failure caused by liver metastasis of malignant tumor. Their clinical manifestations, laboratory markers, clinical progress, and outcome were observed, and the clinical features were summarized. Results: Such patients were manifested as liver enlargement and rapid clinical progression, and imaging examination showed stenosis due to external compression in the inferior vena cava. The patients might be easily misdiagnosed with Budd-Chiari syndrome and had a poor prognosis, with a mortality rate as high as 100%. Conclusion: As for the liver failure patients with unexplained liver enlargement, the possibility of liver metastasis of malignant tumors should be considered. Liver biopsy should be performed as early as possible before the deterioration of liver function, in order to facilitate the targeted therapy for the primary tumor.