['This study aims to determine the role of serum interleukin-6 concentration for oral cavity squamous cell carcinomas.', 'Cohort study.', 'Tertiary referral center.', 'Two hundred thirty-seven untreated patients, 125 healthy individuals, and 104 individuals with oral premalignant lesions were enrolled. Interleukin-6 serum concentrations were measured by enzyme-linked immunosorbent assay.', 'Serum concentrations of interleukin-6 were significantly higher in patients compared with the levels in healthy individuals and the subjects with oral premalignant lesions. Serum interleukin-6 levels were significantly higher in patients with higher pT status (from pT1 to pT4, median values in pg/mL = 0, 0, 1.3, and 5.0, respectively, with P < .001), higher pathological stages (from stage I to IV, median values = 0, 0, 1.3, and 3.6, respectively, with P < .001), positive bone invasion (5.0 vs 0, 1.4 vs 0; P < .001), and higher tumor depths (1.4 vs 0; P = .005). Patients with higher pretreatment levels of interleukin-6 (>1.35 pg/mL, median level) had worse prognoses for 5-year overall survival and disease-specific survival despite treatment (75.7% vs 54.9% and 79.1% vs 59.8%; P = .001 and .003, respectively). Multivariate logistic regression analyses also indicated that higher interleukin-6 serum levels were an independent prognostic factor for overall survival and disease-free survival (adjusted hazard ratio = 2.417 and 2.364; P = .009 and .017, respectively).'] Are pretreatment interleukin-6 serum levels associated with patient survival for oral cavity squamous cell carcinoma?