Objective: To investigate the effects of Gli2 on the proliferation, growth, migration and invasion of oral cancer cells (Tca8113) at the cellular level, and to clarify the molecular mechanism of Gli2 regulation on the migration and invasion of oral cancer cells. Methods: siRNA was used to inhibit Gli2 expression in Tca8113 cells. The effects of Gli2 on the proliferation, growth, migration and invasion of Tca8113 cells were examined by CCK-8, plate cloning and transwell chamber assay. Further, qRT-PCR and Western blot were used to explore the mechanism of Gli2 regulation of malignant proliferation and metastasis of Tca8113 cells. Results: The mRNA and protein expression of Gli2 in oral cancer cells (Tca8113) were increased. Interference with Gli2 expression inhibited the proliferation, growth, migration and invasion of Tca8113 cells. Further studies showed that interfering with Gli2 expression inhibited mRNA and protein expression of key factors in Hedgehog (Hh) pathway. In addition, interference with Gli2 expression can significantly affect mRNA and protein expression of key factors in Epithelial mesenchymal transformation (EMT) pathway. Conclusion: Gli2 is abnormally activated during oral cancer, and interference with Gli2 expression significantly inhibits the proliferation, growth, migration and invasion of oral cancer cells. Gli2 influences the migration and invasion of oral cancer cells by regulating Hh pathway and EMT pathway. This study provides a new way to elucidate the pathogenesis of oral cancer and a new perspective for clinical treatment of oral cancer.