Oral squamous cell carcinoma (OSCC) is the most common malignant tumour in the oral and maxillofacial region, and has a poor prognosis. Cyfra 21-1 is a useful tumour marker for squamous cell carcinoma, but the clinical value of Cyfra 21-1 in OSCC has not been confirmed. In order to investigate the diagnostic and prognostic value of serum Cyfra 21-1 in primary OSCC patients, the preoperative serum Cyfra 21-1 concentration of 100 OSCC patients and 56 healthy subjects was detected by enzyme-linked immunosorbent assay (ELISA). The cut-off value was calculated with a receiver operating characteristic (ROC) curve, and prognostic analysis was performed using the Kaplan-Meier method and Cox regression models. The preoperative serum Cyfra 21-1 concentration in OSCC patients (1.18+/-1.20 microg/L) was significantly higher (t=6.585, P<0.001) than that in healthy subjects (0.40+/-0.16 microg/L). With a cut-off value of 0.65 microg/L, the diagnostic sensitivity and specificity was 0.570 and 0.964, respectively. There was significant correlation with tumour recurrence and survival rate: the higher the serum Cyfra 21-1; the higher the tumour recurrence rate and lower the survival rate. Serum Cyfra 21-1 was an independent prognostic factor for OSCC using univariate and multivariate Cox models.