By integrating bioinformatics, experimental validation, and clinical correlation analyses, we identified six SFs (CRNKL1, SNRPB2, RBMX2, DDX46, PPWD1, and CFAP20) that are aberrantly overexpressed in esophageal cancer and tightly linked to poor prognosis. This evidence concerns the gene RBMX2 and esophageal cancer.