Background: In anal cancer, there are no markers nor other laboratory indexes that can predict prognosis and guide clinical practice for patients treated with concurrent chemoradiation. In this study, we retrospectively investigated the influence of immune inflammation indicators on treatment outcome of anal cancer patients undergoing concurrent chemoradiotherapy. Methods: All patients had a histologically proven diagnosis of squamous cell carcinoma of the anal canal/margin treated with chemoradiotherapy according to the Nigro's regimen. Impact on prognosis of pre-treatment systemic index of inflammation (SII) (platelet x neutrophil/lymphocyte), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were analyzed. Results: A total of 161 consecutive patients were available for the analysis. Response to treatment was the single most important factor for progression-free survival (PFS) and overall survival (OS). At univariate analysis, higher SII level was significantly correlated to lower PFS (p<0.01) and OS (p=0.046). NLR level was significantly correlated to PFS (p=0.05), but not to OS (p=0.06). PLR level significantly affected both PFS (p<0.01) and OS (p=0.02). On multivariate analysis pre-treatment, SII level was significantly correlated to PFS (p=0.0079), but not to OS (p=0.15). We developed and externally validated on a cohort of 147 patients a logistic nomogram using SII, nodal status and pre-treatment Hb levels. Results showed a good predictive ability with C-index of 0.74. An online available calculator has also been developed. Conclusion: The low cost and easy profile in terms of determination and reproducibility make SII a promising tool for prognostic assessment in this oncological setting.