Chemoimmunotherapy has become the first-line treatment for unresectable esophageal squamous cell carcinoma (ESCC). Still, reliable biomarkers to identify patients who could benefit from this combined therapy remain uncertain. This study focused on elucidating the predictive significance of the monocyte-to-lymphocyte ratio (MLR) and establishing the prognostic nomogram for unresectable ESCC treated with chemoimmunotherapy.