FADS1 (fatty acid desaturase 1) plays a crucial role in fatty acid metabolism, and it was recently reportedto be involved in tumorigenesis. However, the role of FADS1 expression in esophageal squamous cell carcinoma(ESCC) remains unknown. In the current study, we investigated the expression and clinical pathologic andprognostic significance of FADS1 in ESCC. Immunohistochemical analyses revealed that 58.2% (146/251) ofthe ESCC tissues had low levels of FADS1 expression, whereas 41.8% (105/251) exhibited high levels of FADS1expression. In positive cases, FADS1 expression was detected in the cytoplasm of cells. Correlation analysesdemonstrated that FADS1 expression was significantly correlated with tumor location (p=0.025) but not withage, gender, histological grade, tumor status, nodal status or TNM staging. Furthermore, patients with tumorsexpressing high levels of FADS1had a longer disease-free survival time (p<0.001) and overall survival time (p<0.001). Univariate and multivariate analyses revealed that, along with nodal status, FADS1 expression was anindependent and significant predictive factor (p<0.001). In conclusion, our study suggested that FADS1 mightbe a valuable biomarker and potential therapeutic target for ESCC.