Abstract: STING and MIF are Tumor-immune related proteins act as immune regulating roles that effect the progression of cancer. In these studies, we aimed to detect the expression levels of STING and MIF in tumor cells and in lymphocytes in tumor microenvironments and their association with survivals of patients diagnosed with esophageal squamous cell carcinoma (ESCC). The expression levels of STING and MIF were accessed by immunochemistry staining in tumor tissues from 112 resected ESCC. Correlation analyses and independent prognostic outcomes were determined using Pearson's chi-square test. Independent prognostic outcomes were measured by Cox regression analysis. We found that STING high expression in TILs or MIF high expression in tumor cells or in tumor infiltrating lymphocytes (TILs) was significantly related to reduced disease-free survival (DFS) and overall survival (OS) of ESCC patients (P<0.05). Multivariate analysis indicated that the expression of STING and MIF in TILs were adverse independent prognostic factors in the whole cohort of patients (P<0.05). The expression of MIF in tumor cells or in TILs was significantly positively correlated with STING in TILs (P<0.05). The combined STING and MIF expression in TILs was strongly related to reduced DFS and OS of ESCC patients (P<0.05). Our studies indicated the expression levels of STING and MIF in TILs were independent predictive factors of survivals in patients with ESCC.