Objective: To examine the level of serum Cyfra21-1 in patients with oral squamous cell carcinoma(OSCC) and to explore the potential application of serum Cyfra21-1 detection in the diagnosis of OSCC. Methods: The serum Cyfra21-1 concentrations were detected by ELISA. Results: The preoperative serum Cyfra21-1 concentration in patients with OSCC was (1.12±0.61) ng/ml, which was significantly higher than that in healthy persons (0.34±0.20) ng/ml and that in patients with oral benign tumor (0.50±0.27) ng/ml. The sensitivity rate and specificity rate of the test were 83.9% and 89.3%, respectively. For 10 patients with OSCC, the serum Cyfra21-1 concentrations were decreased from (1.31±0.25) ng/ml preoperatively to (0.65±0.14) ng/ml postoperatively. Conclusion: Cyfra21-1 may be a good marker in diagnosis of OSCC.