Abstract: Objective: To investigate the effect of PTEN interference on the invasive ability of thyroid follicular epithelial cells (Nthy-ori3-1) and to explore its possible molecular mechanism. Methods: The human normal thyroid follicular epithelial cell Nthy-ori3-1 was useed as the research object, PTEN-targeted shRNA and unrelated sequence-targeted shRNA were transfected into Nthy Ori-3 cells by lentivirus.. The experiment was divided into two groups: the unrelated sequence group (shControl) and the PTEN interference group (shPTEN). The invasion ability of cells was detected by Transwell cell invasion assay. The expression level of invasion related proteins were detected by immunofluorescence. The protein expression level of related proteins were detected by Western blot. Results: Compared with unrelated sequence group, the cell morphology of PTEN interference group changed significantly; Transwell cell invasion assay showed that compared with unrelated sequence group, the invasive ability of interference group was enhanced; immunofluorescence results showed that compared with unrelated sequence group, the expression level of E-Cadherin in PTEN interference group decreased; Western blot results also showed that the E-cadherin protein level significantly decreased in PTEN interference group. Conclusion: PTEN interference can promote the invasion of Nthy-ori3-1 cells, and this effect may be mediated by downregulating expression of E-cadherin.