Objective:To investigate the effect of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in modulat-ing the effects of oral squamous cell carcinoma (OSCC) invasion. Methods:Real-time polymerase chain reaction was employed to de-tect the expression of MALAT1 in samples of OSCC post-radical resection, normal oral mucosa samples, and oral squamous cell lines. MALAT1-siRNA was transfected into TSCCa human tongue squamous cell carcinoma cell lines. Cell proliferation was determined by methyl-thiazolyl-tetrazolium reduction assay. Cell migration and invasive ability were evaluated by scratch test and transwell assay. The expression of proteins that regulated invasion and apoptosis were examined using Western blot assay. Immunofluorescence assay was used to detect changes in epithelial-mesenchymal transition (EMT)-associated proteins in the cells. Tumor-bearing nude mouse models were established by subcutaneous implantation of TSCCa cells. Immunohistochemistry was used to detect up-regulation of proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase-2/9 (MMP-2/9). Results:MALAT1 expression was significantly higher in OSCC than in normal tissues (P<0.05). MALAT1 expression was inhibited by transfecting MALAT1-siRNA. After MALAT1 expres-sion was down-regulated in TSCCa cells, proliferation was inhibited and invasion was attenuated, showing significant differences com-pared with the cells transfected with scrambled siRNA and control cells (P<0.05). Expression of N-cadherin and MMP-2/9 were down-regulated in the cells after MALAT1 was knocked down. Tumor growth was significantly slower in the MALAT1-siRNA group than in the control groups. IHC indicated that PCNA and MMP-2/9 expression of tumor tissues were significantly inhibited in MALAT1-siR-NA group. Conclusion:MALAT1 is over-expressed in human OSCC. MALAT1 reduction can inhibit the proliferation and invasion of OSCC cells. Furthermore, MALAT1 may promote OSCC invasion and metastasis by modulating EMT.