ObjectiveTo investigate the role of CC chemokine ligand 18 (CCL18)membraneassociated phosphatidylinositol transfer protein 3 (PITPNM3) ligand receptor axis in the invasion and metastasis of squamous cell carcinoma of the head and neck (SCCHN) and its molecular mechanism.MethodsHuman recombinant protein CCL18 (rhCCL18) was used to stimulate SCCHN Tu686 and 610B cells. siRNA was used to downregulate the expression of PITPNM3, and the growth and proliferation abilites were detected by cholecystokinin octapeptide (CCK8), cloning formation assays and flow cytometry. The scratch healing assays and Transwell invasion chamber assays were performed to detect changes of migration and invasion abilities in vitro, and the expression of epithelialmesenchymal transition (EMT) molecular markers was detected by quantitative realtime polymerase chain reaction (qRTPCR) and Western blot.Results①In the Tu686 and 610B cells, rhCCL18 stimulation got the cell scratch healing rates increased with significantly elevated numbers of cells passing through Transwell polycarbonate membrane. After rhCCL18 stimulation, the Tu686 and 610B cells with downregulated expression of PITPNM3 by siRNA didn’t show any clear trends in the migration abilities and numbers of cells passing through Transwell polycarbonate membrane as the parental ones did. ②After treatment of Tu686 and 610B cells with rhCCL18, the expressions of Ecadherin at both mRNA level and protein level decreased, while the expressions of Vimentin at both levels and those of Ncadherin and Fibronectin at mRNA level increased. After rhCCL18 treatment, Tu686 and 610B cells with downregulated expression of PITPNM3 by siRNA didn’t show any clear trends in the expressions of Ecadherin, Vimentin, Ncadherin and Fibronectin as the parental ones did. ③The results of CCK8, cloning formation and flow cytometry indicated that rhCCL18 stimulation and downregulation of PITPNM3 did not lead to significant changes in the growth rates and proliferation as well as cell cycles of Tu686 and 610B cells.ConclusionCCL18PITPNM3 ligand receptor axis can promote the in vitro invasive and metastatic abilities of SCCHN, which may be related to EMT.