A previous study indicated that C–C chemokine(C–C motif)ligand 18(CCL18)is capable of inducing tumor cell invasion and metastasis by interacting with receptor membrane-associated phosphatidylinositol transfer protein 3(PITPNM3)in breast cancer cells.The present study aims to investigate the correlation between the PITPNM3 expression and metastasis in hepatocellular carcinoma(HCC).Real-time quantitative polymerase chain reaction and Western blot were performed to detect the expression pattern of PITPNM3 in patient samples and HCC cell lines.Wound-healing and transwell chamber assays were performed to assess the migration and invasiveness of HCC cells,and the activation of the signaling protein downstream of PITPNM3 was also detected by Western blot and immunofluorescence.The results revealed that PITPNM3 was upregulated in HCC tissue compared to matched normal liver tissue.Silencing the expression of PITPNM3 by specific siRNAs markedly attenuated the invasive and metastatic abilities of HCC cells,whereas the upregulation of PITPNM3 significantly increased HCC cell mobility.Furthermore,inhibiting the expression of PITPNM3 suppressed the activation of Pyk2,FAK,and Src,while overexpression of PITPNM3enhanced the phosphorylation of FAK and Src in HCC cells.Besides,suppression of Pyk2 can also impair the clustering of integrin.These results imply that PITPNM3 is a vital determinant of HCC migration and invasion. Previous study indicated that C-C chemokine (C-C motif) ligand 18 (CCL18) is capable of inducing tumor cell invasion and metastasis by interacting with receptor membrane-associated phosphatidylinositol transfer protein 3 (PITPNM3) in breast cancer cells. Present analysis aims to investigate the correlation between the PITPNM3 expression and metastasis in hepatocellular carcinoma (HCC). Real-time quantitative polymerase chain reaction and Western blot were performed to detect the expression pattern of PITPNM3 in patient samples and HCC cell lines. transwell chamber assays were performed to assess the migration and invasiveness of HCC cells, and the activation of the signaling protein downstream of PITPNM3 was also detected by Western blot and immunofluorescence. The results revealed that PITPNM3 was upregulated in HCC tissue compared to matched normal liver tissue . Silencing the expression of PITPNM3 by specific siRNAs markedly attenuated the invasive and metastatic abilitie s of HCC cells, and the upregulation of PITPNM3 significantly increased HCC cell mobility. Frther of inhibiting the expression of PITPNM3 suppressed the activation of Pyk2, FAK, and Src, while overexpression of PITPNM3 enhanced phosphorylation of FAK and Src in HCC cells. suppression of Pyk2 can also impair the clustering of integrin.These results imply that PITPNM3 is a vital determinant of HCC migration and invasion.