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Objective: Pretreatment systemic inflammation and nutrition‐based prognostic indices (SINBPI) have demonstrated significance. This study investigated the prognostic value of pretreatment SINBPI for patients with oropharyngeal cancer and identified unfavorable prognostic markers. Methods: We retrospectively reviewed the data of 124 patients with oropharyngeal squamous cell carcinoma (OPSCC) who received definitive treatment between January 2010 and December 2018. The prognostic utility of the neutrophil‐to‐lymphocyte ratio, platelet‐to‐lymphocyte ratio (PLR), lymphocyte‐to‐monocyte ratio (LMR), prognostic nutritional index, and high‐sensitivity modified Glasgow prognostic score (HS‐mGPS) was assessed for disease‐free survival (DFS), disease‐specific survival (DSS), and overall survival (OS) using univariate and multivariate analyses. Results: Multivariate analyses revealed that human papillomavirus (HPV) status and HS‐mGPS were significantly associated with DFS, DSS, and OS. Patients with a HS‐mGPS of 2 had a significantly higher rate of treatment‐related deaths than those with a HS‐mGPS of 0 or 1. The combination of the HS‐mGPS and PLR had more accurate predictive ability in DFS and OS compared with the HS‐mGPS alone, and the combination of the HS‐mGPS and LMR had more accurate predictive ability in DSS and OS. Conclusion: Our results indicated that the HS‐mGPS was a useful prognostic marker for patients with OPSCC, and combined markers consisting of the HS‐mGPS and PLR or LMR may provide more accurate prognostic predictions. Level of Evidence: 3. [ABSTRACT FROM AUTHOR]