Purpose <p>This study aims to provide a simple indicator for predicting the prognosis of cancer survivors and offer reference and guidance for management strategies to ultimately improve their long-term prognosis.</p> Methods <p>Based on data from the 1999–2019 National Health and Nutrition Examination Survey, we included 3436 cancer survivors in this study. Participants were defined as cancer survivors if they had been previously diagnosed with cancer by a doctor or health professional. The neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and systemic inflammatory response index (SIRI) were used as systemic inflammatory markers. Survival status was determined by linking it with National Death Index records. Associations between systemic inflammatory markers and cancer survivor prognoses were evaluated using weighted Cox regression, Kaplan–Meier survival curves, and restricted cubic spline curves.</p> Results <p>All three systemic inflammatory markers were significantly associated with cancer survivor prognoses after adjusting for confounders. NLR and SIRI were positively associated with all-cause mortality (ACM), while LMR was negatively associated with ACM in cancer survivors. The hazard ratios and 95% confidence interval were 1.10 (1.07–1.14), 1.16 (1.10–1.21) and 0.91 (0.87–0.95) respectively. In addition, a significant nonlinear correlation was observed between LMR and the prognosis of cancer survivors (P for nonlinear &lt; 0.05).</p> Conclusions <p>NLR, SIRI, and LMR were independent predictors of prognosis in cancer survivors. NLR and SIRI were positively associated with ACM, while LMR was negatively associated with ACM.</p> Implications for cancer survivors <p>Systemic inflammatory markers may help predict outcomes and inform care strategies for cancer survivors.</p>