Raf kinase inhibitory protein (RKIP) belongs to the phosphatidylethanolamine binding protein family. RKIP is an endogenous inhibitor of the ERK/MAPK, NF-κΒ, and G protein-coupled receptor signaling pathways. This study aims to investigate the expression of RKIP in non-small cell lung cancer (NSCLC) and to determine the association of RKIP expression with the clinicopathologic features of NSCLC.Reverse transcription-polymerase chain reaction, Western blot, and immunohistochemistry were used to detect RKIP expression in 83 specimens with NSCLC and normal lung tissues and to analyze the association of RKIP expression with the clinicopathologic features of NSCLC. All cases were confirmed by pathological diagnosis, and primary tumors were not found at other sites. No medical records of preoperative radiotherapy, chemotherapy, and immunotherapy were found in the groups.RKIP expression was down-regulated significantly in NSCLC compared with adjacent cancer tissues (P0.05).The deficiency of RKIP expression is positively correlated with carcinogenesis and invasion metastasis of NSCLC. RKIP is a potential marker and target for clinic therapy.