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Esophageal squamous cell carcinoma (ESCC) is a life-threatening thoracic tumor with a poor prognosis. The role of molecular alterations and the immune microenvironment in ESCC development has not been fully elucidated. The present study aimed to elucidate key candidate genes and immune cell infiltration characteristics in ESCC by integrated bioinformatics analysis. Nine gene expression datasets from the Gene Expression Omnibus (GEO) database were analysed to identify robust differentially expressed genes (DEGs) using the robust rank aggregation (RRA) algorithm. Functional enrichment analyses showed that the 152 robust DEGs are involved in multiple processes in the tumor microenvironment (TME). Immune cell infiltration analysis based on the 9 normalized GEO microarray datasets was conducted with the CIBERSORT algorithm. The changes in macrophages between ESCC and normal tissues were particularly obvious. In ESCC tissues, M0 and M1 macrophages were increased dramatically, while M2 macrophages were decreased. A robust DEG-based protein–protein interaction (PPI) network was used for hub gene selection with the CytoHubba plugin in Cytoscape. Nine hub genes (CDA, CXCL1, IGFBP3, MMP3, MMP11, PLAU, SERPINE1, SPP1 and VCAN) had high diagnostic efficiency for ESCC according to receiver operating characteristic (ROC) curve analysis. The expression of all hub genes except MMP3 and PLAU was significantly related to macrophage infiltration. Univariate and multivariate regression analyses showed that a 7-gene signature constructed from the robust DEGs was useful for predicting ESCC prognosis. Our results might facilitate the exploration of potential targeted TME therapies and prognostic evaluation in ESCC. [ABSTRACT FROM AUTHOR]