Integrins mediate cell-extracellular matrix (ECM) interaction and play a critical role in cell proliferation, migration, survival, and invasion. Polymorphisms of the Integrin gene can alter integrin protein expression, which may further increase the risk of malignancies or cause poor clinical outcomes. The aim of this study was to investigate the potential associations of single-nucleotide polymorphisms (SNPs) of the integrin gene with the susceptibility and clinicopathologic parameters of oral squamous cell carcinoma (OSCC). Two hundred patients with OSCC and 200 healthy volunteers were recruited. Five SNPs of Integrin genes were analyzed by polymerase chain reaction-restriction fragment length polymorphism genotyping. Their correlations with OSCC risk and clinical tumor characteristics were evaluated. The AT genotype of rs3809865 and GC genotype of rs1190271 increased the risk of OSCC by 2.1-fold (95% confidence interval 1.323-3.829, P=0.004) and 2.85-fold (95% confidence interval 1.583-5.138, P<0.01), respectively. Cases with AT genotype of rs3809865 and GC genotype of rs11902171 were prone to have regional lymph nodes metastasis (P<0.01). The SNPs of rs3809865 and rs1190271 might contribute to the prediction of susceptibility and lymph node metastasis of OSCC, which should be thought as a diagnostic marker and a potential therapeutic target.