Lysyl oxidase (LOX) is a copper-dependent enzyme that cross-links collagen and elastin in the extracellular matrix. LOX overexpressed in various tumors. The manner in which LOX affects tumor growth remains controversial. Chemical treatment and gene transfection were used to induce LOX overexpression or inhibition in cell lines SAS and SVEC4-10. LOX mRNA, protein, and activity were confirmed before tube formation assay and tumorigenesis. The microvessels in the tumor section were detected by immunostaining CD31-positive endothelial cells. LOX overexpression and copper induction of LOX activity increased SVEC4-10 tube formation. LOX silencing and β-aminopropionitrile inhibition of LOX activity had opposite effects. LOX overexpression increased proliferation and proliferating cell nuclear antigen expression. High LOX expression clones increased tumor size in a tumorigenesis model. The microvascular numbers were higher in LOX overexpression tumors than in control tumors. LOX can induce cell proliferation and angiogenesis in oral squamous cell carcinoma.