Objective: Programmed cell death ligand-1 interacts with the immune receptors on the surface of CD8+ tumor infiltrating lymphocytes and PD-1, thereby blocking its anti-tumor activity. Therapeutics suppression of this interaction will show a promise in the treatment of non-small cell lung cancer by restoring the functional anti-tumor T-cell activity. We aimed to evaluate the association between the immunohistochemical expression of PD-L1, stromal CD8+ tumor infiltrating lymphocytes and p53 with clinicopathological characteristics, response to chemotherapy, progression-free-survival, and overall survival. Materials and Methods: We examined the immunohistochemical expression of PD-L1, stromal CD8+ TILs, and P53 expression in 50 patients with advanced stage (III&IV) non-small cell lung cancer. Results: PD-L1 was expressed in 56% of the studied cases. PD-L1 expression was related to unfavorable response to the therapy without significant difference. PD-L1 expression was significantly associated with disease progression, poor progression-free-survival & overall survival. CD8+ TILs were high in 32% of the cases. Tumors with high CD8+ TILs showed a partial response to therapy and had a better progression-free-survival and overall survival. P53 expressed in 82% of the studied cases. There was a significant negative association between PD-L1 and CD8+ TILs (p=0.009), while a non-significant association was found between p53 and PD-L1 (p=0.183). Conclusion: PD-L1 overexpression is an unfavorable prognostic marker, while the high CD8 + TILs is a good prognostic marker in non-small cell lung cancer. PD-L1 immunohistochemical assessment may be used for the selection of patients legible for treatment with anti-PD-L1 therapy.