Purpose: Epithelial cell transforming sequence 2 (ECT2) is a guanine nucleotide exchange factor, which is involved in cell division regulation and cell cycle modulation. Recent evidence indicates that ECT2 is overexpressed in many human cancers. However, the exact prognostic value of ECT2 in lung cancer has not been elucidated. Patients and methods: In the current study, we performed correlation and prognosis analyses using public databases and conducted immunohistochemical staining in tissue microarrays, using samples from 204 lung cancer patients with survival data. Results: We found that the expression of ECT2 was markedly increased in lung cancer tissues compared with normal tissues. Moreover, we demonstrated that the expression of ECT2 was related to tumor cell differentiation degree, TNM stage, lymph node metastasis, and prognosis in non-small-cell lung cancer (NSCLC). A correlation analysis indicated that ECT2 levels were significantly correlated with proliferating cell nuclear antigen (PCNA) levels in NSCLC. Furthermore, Kaplan-Meier analyses revealed that high ECT2 expression was associated with unfavorable overall survival (OS) and progression-free survival (PFS) in NSCLC patients. Conclusion: Taken together, these results indicate that the overexpression of ECT2 contributes to tumor invasion and progression, suggesting that ECT2 is a potential prognostic marker for NSCLC patients.