Objective The effect and mechanism of Galectin-3 gene expression on proliferation, invasion, and apoptosis of oral squamous cell carcinoma (OSCC) were investigated. Methods Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to detect the mRNA and protein of Galectin-3 gene in OSCC. OSCC Tca8113 was divided into control, negative control, and Galectin-3 transfection groups. Western blotting was used to detect the expression of Galectin-3, matrix metalloproteinase (MMP)-2, MMP-9, Cleaved Caspase-3, β-catenin, and Cyclin D1 protein after transfection for 48 h in each group. Cell proliferation was detected by CCK8. Cell invasion ability was detected by using a Transwell chamber. Cell apoptosis was detected by flow cytometry. Results The mRNA and protein expression levels of Galectin-3 gene in OSCC were significantly higher than those in adjacent tissues (P<0.01). Galectin-3 protein expression in Tca8113 cells significantly decreased after RNA interference. Cell survival rate and invasion as well as MMP-2, MMP-9, β-catenin, and Cyclin D1 protein expression were significantly lower than the blank group. Apoptosis rate and Cleaved Caspase-3 protein expression were sig-nificantly higher than the control group (P<0.01). Conclusion Inhibition of Galectin-3 gene expression in OSCC can signi-ficantly reduce the proliferation and invasion of cancer cells and induce apoptosis. The mechanism is related to downregulation of the Wnt/β-catenin signaling pathway.