Various systemic inflammation indices have emerged as prognostic markers for renal cell carcinoma (RCC); however, these indices have not been comprehensively integrated. In this study, we propose a novel systemic inflammation indice, the platelet-neutrophil-monocyte-lymphocyte ratio (PNMLR), aimed at more accurately assessing survival outcomes of patients with non-metastatic RCC.We conducted a retrospective analysis of non-metastatic RCC patients who underwent nephrectomy between 2009 and 2013. Restricted cubic splines (RCS) were used to observe the relationship between PNMLR and disease-free survival (DFS) as well as overall survival (OS). Receiver operating characteristic curve and the Maximally Selected Log-Rank Statistic were employed to determine the optimal cutoff value of PNMLR. Patients were then divided into two groups based on the determined cutoff values and propensity score matching (PSM) was performed to balance baseline characteristics. After that, Kaplan-Meier curves and cox regression models were utilized to evaluate DFS and OS. Finally, the concordance index (c-index) of PLNMR (before PSM) in predicting DFS and OS was calculated and compared with other systemic inflammation indices.A total of 1163 patients were included. RCS showed a significant association between PNMLR and DFS as well as OS (both p < 0.001). The optimized PNMLR cutoff was 168. Patients with higher PNMLR exhibited larger tumor size (OR = 1.16, p = 0.028), higher Fuhrman grade (HR = 1.59, p = 0.001), and advanced pT stage (HR = 1.88, p = 0.003). After PSM, elevated PNMLR was associated with poorer DFS (HR = 1.56, p = 0.011) and OS (HR = 1.75, p = 0.004). The c-index of PNMLR for DFS and OS were 0.643 (95%CI, 0.596-0.689) and 0.669 (95%CI, 0.611-0.708) respectively, suggesting competitive predictive performance compared to other systemic inflammation indices.PNMLR is a promising prognostic marker for non-metastatic RCC. However, its moderate discriminative ability suggests that PNMLR should be used in conjunction with other established clinical parameters. Further validation, particularly in independent, contemporary external cohorts, is essential to fully harness its clinical utility.© 2025. The Author(s).