Background/Objectives: Chronic inflammation significantly contributes to human malignancies. We investigated the prognostic significance of the preoperative modified systemic inflammation score (mSIS) in patients with primary oral cavity squamous cell carcinoma (OCSCC). Methods: We retrospectively reviewed data from 320 OCSCC patients who underwent curative surgery between 2007 and 2017. Based on preoperative lymphocyte-to-monocyte ratio (LMR) and serum albumin levels, patients were classified into three groups: mSIS = 2 (LMR n = 197, 61.6%), mSIS = 1 (n = 99, 30.9%), and mSIS = 2 (n = 24, 7.5%). Kaplan–Meier estimated OS and DFS for the mSIS = 0, mSIS = 1, and mSIS = 2 groups demonstrated a sequential decrease (both p < 0.001). The prognostic significance of mSIS was consistent across subgroup analyses. Multivariable analysis revealed that mSIS = 1 and mSIS = 2 were independent negative prognostic indicators. The mSIS-based nomogram effectively predicted OS (concordance index: 0.755). Conclusions: The mSIS reliably predicts OS and DFS in OCSCC patients undergoing surgery, with the nomogram providing individualized OS estimates, enhancing mSIS’s clinical utility.
