It has been recognized that systemic inflammatory markers (SIMs) are associated with patient survival in various types of cancer. This study aimed to determine the optimal cut-off values, and to evaluate the prognostic performance of SIMs for oral squamous cell carcinoma (OSCC) within the framework of the American Joint Committee of Cancer (AJCC) cancer staging manual, 8th edition. Records were collected for a total 291 patients who had had a peripheral blood test within 1 week prior to surgery and had undergone the surgical resection of OSCC in a single institution between 2005 and 2018. The cut-off values of SIMs were obtained, and the survival analyses for overall survival (OS) and disease-free survival (DFS) were performed. Multivariate analyses incorporating other clinicopathologic factors were performed to verify the independent risk factors for survival. The cut-off values of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were 2.23, 135.14 for OS and 2.16, 131.07 for DFS, respectively, demonstrating a significant association for OS and DFS in OSCC. AJCC pathologic regional lymph node category (pN) (P < 0.001), perineural invasion (PNI) (P < 0.001) and NLR (P < 0.001) were independent predictors for OS. Meanwhile, for DFS, AJCC pN (P = 0.018) and NLR (P = 0.015) were shown to be independent predictors. Before the curative surgery, NLR and PLR could be auxiliary parameters for OS and DFS in OSCC. And based on the 8th edition of AJCC staging system, elevated NLR will be a potential indicator of the worse OS or DFS along with pN or PNI in OSCC.