Background: Discs large homolog 5 (Dlg5) is a newly discovered member of the membrane-associated guanylate kinase superfamily (MAGUK) that is involved in several important processes, including the maintenance of epithelial cell polarity, cell proliferation control, and cell migration and invasion. Decreased expression of Dlg5 has been reported in malignancies arising from different organs. In the present study, we analyzed Dlg5 expression and its prognostic value in squamous cell lung cancer (SqCLC). Methods: Tumor tissue and adjacent normal tissue sections were collected from 98 patients with SqCLC. The expression levels of Dlg5 and epithelial-mesenchymal transition (EMT) biomarkers in the tissue sections were examined by immunohistochemistry and western blot. Results: There were 80 males and 18 females in the study cohort. Patients at pathological stages I and IIIA accounted for 64.3% and 35.7% of the cohort, respectively. Western blot showed that Dlg5 expression differed between SqCLC and healthy tissues. Western blot also revealed low Dlg5 expression to be associated with low E-cadherin expression and high vimentin expression, which was consistent with the findings of immunohistochemical staining. Dlg5 expression was significantly correlated with lymph node (LN) metastasis (P=0.001) and disease recurrence (P<0.001), as well as with E-cadherin and vimentin expression (P=0.025 and P=0.001, respectively). Univariate analysis showed that overall survival was significantly correlated with the tumor-node-metastasis (P<0.001) and T (P=0.001) stages, LN metastasis (P<0.001), Dig5 expression (P<0.001), 0-catenin expression (P=0.004), and vimentin expression (P=0.002). Patients with overexpression of Dlg5 and 0-catenin had a more favorable prognosis than those without. Multivariate analysis revealed that tumor-node-metastasis stage [hazard ratio (HR) =2.124; 95% confidence interval (CI), 1.195-3.777; P=0.010], Dlg5 expression (HR =0.548; 95% CI, 0.313-0.959; P=0.035), 0-catenin expression (HR =0.545; 95% CI, 0.312-0.953; P=0.033), and vimentin expression (HR =1.850; 95% CI, 1.050-3.258; P=0.033) could all independently predict the overall survival of patients with SqCLC. Conclusions: Dlg5 is an important player in EMT which may have potential predictive value for SqCLC prognosis after surgery. Background: Discs large homolog 5 (Dlg5) is a newly discovered member of the membrane-associated guanylate kinase superfamily (MAGUK) that is involved in several important processes, including the maintenance of epithelial cell polarity, cell proliferation control, and cell migration and invasion. Decreased expression of Dlg5 has been reported in malignancies arising from different organs. In the present study, we analyzed Dlg5 expression and its prognostic value in squamous cell lung cancer (SqCLC). Methods: Tumor tissue and adjacent normal tissue sections were collected from 98 patients with SqCLC. The expression levels of Dlg5 and epithelial-mesenchymal transition (EMT) biomarkers in the tissue sections were examined by immunohistochemistry and western blot. Results: There were 80 males and 18 females in the study cohort. Patients at pathological stages I and IIIA accounted for 64.3% and 35.7% of the cohort, respectively. Western blot showed that Dlg5 expression differed between SqCLC and healthy tissues. Western blot also revealed low Dlg5 expression to be associated with low E-cadherin expression and high vimentin expression, which was consistent with the findings of immunohistochemical staining. Dlg5 expression was significantly correlated with lymph node (LN) metastasis (P=0.001) and disease recurrence (P<0.001), as well as with E-cadherin and vimentin expression (P=0.025 and P=0.001, respectively). Univariate analysis showed that overall survival was significantly correlated with the tumor-node-metastasis (P<0.001) and T (P=0.001) stages, LN metastasis (P<0.001), Dig5 expression (P<0.001), 0-catenin expression (P=0.004), and vimentin expression (P=0.002). Patients with overexpression of Dlg5 and 0-catenin had a more favorable prognosis than those without. Multivariate analysis revealed that tumor-node-metastasis stage [hazard ratio (HR) =2.124; 95% confidence interval (CI), 1.195-3.777; P=0.010], Dlg5 expression (HR =0.548; 95% CI, 0.313-0.959; P=0.035), 0-catenin expression (HR =0.545; 95% CI, 0.312-0.953; P=0.033), and vimentin expression (HR =1.850; 95% CI, 1.050-3.258;