Simple SummaryWe introduced a novel squamous cell carcinoma inflammatory index (SCI) derived by multiplying the serum squamous cell carcinoma antigen and neutrophil-to-lymphocyte ratio values for individuals with operable oral cavity squamous cell carcinomas (OSCCs). The prognostic value of SCI was explored by retrospectively analyzing data from 288 patients with a diagnosis of primary OSCC between January 2008 and December 2017. The current results demonstrated that patients with a high SCI (≥3.45) were associated with worse disease-free survival and overall survival than those with a low SCI (<3.45). An elevated preoperative SCI (≥3.45) predicted adverse overall survival (hazard ratio [HR] = 2.378;p< 0.002) and disease-free survival (HR = 2.219;p< 0.001) in a multivariable analysis. The constructed nomogram enables the clinical utility of the SCI and provides accurate OS predictions. Our findings indicate that SCI is a valuable and promising biomarker that is highly associated with patient survival outcomes in OSCC.AbstractWe introduced a novel squamous cell carcinoma inflammatory index (SCI) and explored its prognostic utility for individuals with operable oral cavity squamous cell carcinomas (OSCCs). We retrospectively analyzed data from 288 patients who were given a diagnosis of primary OSCC from January 2008 to December 2017. The SCI value was derived by multiplying the serum squamous cell carcinoma antigen and neutrophil-to-lymphocyte ratio values. We appraised the associations of the SCI with survival outcomes by performing Cox proportional hazards and Kaplan–Meier analyses. We constructed a nomogram for survival predictions by incorporating independent prognostic factors in a multivariable analysis. By executing a receiver operating characteristic curve analysis, we identified the SCI cutoff to be 3.45, and 188 and 100 patients had SCI values of <3.45 and ≥3.45, respectively. The patients with a high SCI (≥3.45) were associated with worse disease-free survival and overall survival than those with a low SCI (<3.45). An elevated preoperative SCI (≥3.45) predicted adverse overall survival (hazard ratio [HR] = 2.378;p< 0.002) and disease-free survival (HR = 2.219;p< 0.001). The SCI-based nomogram accurately predicted overall survival (concordance index: 0.779). Our findings indicate that SCI is a valuable biomarker that is highly associated with patient survival outcomes in OSCC.