〔Abstract〕 To investigate the mechanism of Dipeptidyl peptidase 7 (DPP7) in hepatocellular carcinoma (HCC). Methods The expression of DPP7 protein in hepatocellular carcinoma tissues and liver benign tissues was detected by UALCAN and GEPIA database, immunohistochemical, and Western blot, and its relationship with clinicopathological characteristics was analyzed. The expression of DPP7 was silenced by siRNA and the protein expression of DPP7 in MHCC97H cells was detected by Western blot and qPCR. MTTassay, colony formation assay and wound healing assay were used to detect cell proliferation. Transwell assay was used to detect the invasion and migration ability of cells. Western blot was used to detect the changes of protein markers related to Epithelial-mesenchymal transition (EMT). Results In UALCAN, GEPIA and clinical liver tissue samples, DPP7 expression was upregulated and it was closely related to TNM stage (P=0.002), lymph node metastasis (P=0.038) and depth of tumor invasion (P=0.027). The downregulation of DPP7 protein expression in MHCC97H cells was detected after transfection of siRNA in the experimental group (P < 0.01); Furthermore, the results of the MTT, colony formation, wound healing and Transwell assay demonstrated that knockdown of DPP7 expression in the MHCC97H cell line significantly inhibited the proliferative and metastatic capabilities of these cells. Consistent with this phenotypic change, analysis of epithelial-mesenchymal transition (EMT) related proteins revealed a significant upregulation of the epithelial marker E-cadherin (P<0.001) and downregulation of the mesenchymal markers Vimentin and N-cadherin (P<0.01).