Emperipolesis has been widely described in patients with autoimmune hepatitis, but the significance and the diagnostic value have not been quantitated. The goal of this study was to define the features and clinical significance of emperipolesis in autoimmune hepatitis (AIH). A retrospective histological evaluation of 101 patients with AIH and 184 controls was performed. Confocal staining for CD4, CD8, CD19, CD56, CD163, and CD11b, CK8/18 and cleaved caspase-3 was performed. Emperipolesis was observed in 65.3 % of the patients with AIH in haematoxylin and eosin (H&E)-stained slides, which was significantly higher than in patients with primary biliary cirrhosis (17.9 %), chronic hepatitis B (14.9 %), and drug-induced liver injury (25.6 %). Among AIH patients, the patients with emperipolesis had significantly higher serum (alanine aminotransferase/aspartate aminotransferase [ALT/AST]) levels. Histologically, emperipolesis was associated with more severe necroinflammatory features and more advanced fibrosis. The lymphocytes in hepatocytes were predominantly as CD8 T cells. Emperipolesis of CD8 T cells induced cleaved caspase-3 expression, and was prominent in areas apoptosis. Emperipolesis is a characteristic feature of AIH which is often seen in conjunction with interface hepatitis, plasmacytic infiltration and hepatocyte rosetting and is associated with more severe necroinflammatory and fibrotic changes. In AIH, emperipolesis is predominantly mediated by CD8 T cells, appears to induce apoptosis and may be another mechanism of autoimmune-mediated hepatocyte injury.