Objective:To investigate the expression and correlation of EHD2 and E-cadherin in hepatocellular carcinoma (HCC). Meth-ods:Western blot and immunohistochemistry were used to detect the expression of EHD2 and E-cadherin in HCC specimens and adja-cent noncancerous tissues. The correlations of EHD2 and E-cadherin with the clinicopathological characteristics and prognosis of pa-tients were further analyzed using Pearsonχ2 test and Kaplan-Meier method. Results:EHD2 expression, along with E-cadherin, was markedly reduced in HCC tissues than in adjacent noncancerous tissues. Moreover, EHD2 and E-cadherin expression were correlated with histological grade, microvascular invasion, and lymph node metastasis (P<0.05). Kaplan-Meier survival analysis showed that HCC patients with decreased EHD2 and E-cadherin expression had shorter overall survival time than those with higher expression. Conclu-sion:The abnormal expression of EHD2 and E-cadherin possibly promote HCC. Detection of EHD2 and E-cadherin may be valuable for diagnosing HCC and evaluating malignancy extent and prognosis.