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We have demonstrated that salivary interleukin-6 (IL-6) concentrations change during the treatment in patients with oral squamous cell carcinoma (OSCC). We sought to elucidate the correlations between salivary IL-6 concentration and early locoregional recurrence in OSCC.Stimulated saliva was collected before and after surgery from 27 consecutive patients with OSCC. Recurrence-free survival (RFS) curves were plotted using the Kaplan–Meier method.Of the 27 patients, 11 (41%) were diagnosed with locoregional recurrence within 24 months postsurgery. The median concentrations of IL-6 presurgery and postsurgery were 2.8 pg/mL and 2.1 pg/mL, respectively. The median postsurgery concentration of IL-6 was significantly higher in patients with than without locoregional recurrence (p= .02). Multivariate analysis revealed that postsurgery salivary IL-6 concentration was an independent risk factor for locoregional recurrence (p= .03; risk ratio, 0.14).Posttreatment concentration of salivary IL-6 may predict early locoregional recurrence in OSCC.