Abstract: Objective: To investigate the expression and significance of integrin-linked kinase (ILK) and nitric oxide synthase (NOS) in oral squamous cell carcinoma (OSCC). Methods: 71 cases of tumor and adjacent tissues of patients with OSCC undergoing surgical resection were collected. The expression of ILK, eNOS and iNOS in tumor and adjacent tissues were detected by immunohistochemistry. Results: The positive expression rates of ILK, eNOS and iNOS in adjacent tissues were 39.4%, 45.1% and 29.6%, and most of them were weakly positive, while in OSCC tissues were 98.6%, 93.0% and 95.8%, and most of them were strongly positive. The expression levels of ILK, eNOS and iNOS in OSCC tissues were significantly higher than the adjacent tissues (P<0.05). The expression levels of ILK and iNOS in OSCC tissues were correlated with the degree of cell differentiation and lymph node metastasis (P<0.05). Spearman correlation analysis showed that the expression of ILK in OSCC tissues was positively correlated with the expression of iNOS (r=0.529, P=0.000). Conclusion: Up-regulated expression of ILK, eNOS and iNOS in OSCC might be involved in the cell invasion and metastasis through promoting tumor angiogenesis.