Background: Epidermal growth factor-like domain 7 (Egfl7), a primary endothelial-specific secreted factor, is involved in tumourigenesis in multiple epithelial tumors. However, the role of Egfl7 in laryngeal squamous cell carcinoma (LSCC) has rarely been reported. Method: We determined the expression levels of Egfl7 from 33 fresh and 116 paraffin-embedded samples, analyzed its correlation with clinicopathological parameters, and further investigated its role in promoting proliferation and invasion in vitro. Results: Both mRNA and protein levels of Egfl7 was up-regulated, with 94 (81.03%) samples staining positive for Egfl7. Moreover, Egfl7 expression was significantly correlated with tumor stage (P=0.001), lymph node metastasis (P=0.002) and microvessel density (r=0.623, P<0.001, Spearman's correlation coefficient). Kaplan-Meier analysis revealed that Egfl7 expression was significantly associated with worse disease-free survival (P=0.011) and overall survival (P=0.004) rates. In multivariable Cox regression analysis, Egfl7 expression (P=0.012) was an independent prognostic factor for LSCC. In vitro, siRNA mediated knockdown of Egfl7 resulted in marked decreases in cell viability and invasion, which was accompanied by the S-phase-specific cell cycle blockage and increases of apoptosis. Conclusion: Egfl7 expression was tightly associated with more aggressive tumor behavior and a poor prognosis, indicating that Egfl7 is a valuable predictive marker and a potential therapeutic target for LSCC.