BACKGROUND: The long non-coding RNA FOXD2-AS1 is highly expressed in non-small cell lung cancer and promotes malignant progression. However, the role of FOXD2-AS1 in esophageal squamous cell carcinoma (ESCC) is still unclear. OBJECTIVE: In this study, we examined the relationships between the expression level of FOXD2-AS1 and the outcome of ESCC patients. METHODS: Expression of FOXD2-AS1 was evaluated in cancer tissue and adjacent non-tumor tissue samples from 147 ESCC patients who received radical surgical resection using qRT-PCR. The correlations between the expression level of FOXD2-AS1 and patients' overall (OS) and disease free survival (DFS) were analyzed. RESULTS: FOXD2-AS1 expression was upregulated in ESCC tissue than that in adjacent non-tumor tissue samples (P < 0.001). Kaplan-Meier analysis showed that high FOXD2-AS1 expression was correlated with poor prognosis in ESCC patients. Patients with a high level of FOXD2-AS1 had a shorter OS and DFS than those with a low level of FOXD2-AS1 (P = 0.005 and 0.0001, respectively). On multivariate analysis, the hazard ratio of FOXD2-AS1 expression was 1.66 (95% CI = 1.04-2.64, P = 0.033) for OS and 2.68 (95% CI = 1.49-4.82, P = 0.001) for DFS. CONCLUSIONS: Overall, our results provided convinced evidence that FOXD2-AS1 may serve as a predictive marker for ESCC patients' survival.