Background Esophageal cancer (ESCA) is one of the most common cancers in the digestive tract. Approximately 300000 people on an average die of ESCA per year worldwide. The determination of key microRNAs for the prognosis of ESCA is of indispensable significance in the clinical treatment. Methods The differentially expressed microRNAs were screened by analyzing The Cancer Genome Atlas (TCGA) database. By using the survival data of the database, we analyzed correlation between patients’ survival time and miR-550a expression levels. Differential expression analysis and gene set enrichment analysis were performed using the targeted data. Results It was found that patients with high miR-550a expression levels had shorter survival time. Data mining and signal pathway enrichment analysis of TCGA database showed that abnormal miR-550a expressions affected the recurrence of tumors by the muscle system regulation. Conclusions Through the proposed investigation, miR-550a is found to be a potential biomarker as well as non-coding therapeutic target for esophagus cancer. These results suggest that miR-550a may serve as a therapeutic target and predictor for ESCA survival.