Targeting T-Cell Immunoreceptor with Ig and ITIM domain-poliovirus receptor (PVR) pathway is a potential therapeutic strategy in lung cancer. We analyzed the expression of PVR and programmed death ligand-1 (PD-L1) in surgically resected squamous cell lung carcinoma (SQCC) and determined its prognostic significance. We collected archival surgical specimens and data of 259 patients with SQCC at Yonsei Cancer Center (1998-2020). Analysis of variance was used to analyze the correlations between PVR and PD-L1 expression and patient characteristics. Kaplan-Meier curves were used to estimate recurrence-free survival (RFS) and overall survival (OS). Most patients were male (93%); the majority were diagnosed with stage 1 (47%), followed by stage 2 (29%) and stage 3 (21%). Overexpression of PVR resulted in a significantly shorter median RFS and OS (P = 0.01). PD-L1 expression was not significant in terms of prognosis. Patients were subdivided into four groups based on low and high PVR and PD-L1 expression. Those expressing high levels of PVR and PD-L1 had the shortest RFS (P = 0.03). PVR overexpression is associated with a poor prognosis in surgically resected SQCC. Inhibition of PVR as well as PD-L1 may help overcome the lack of response to immune checkpoint monotherapy.