The aim of this study was to characterize variations in Raf kinase inhibitor protein (RKIP) expression and related signaling molecules in gastric cardia adenocarcinoma. Cancerous and precancerous tissues were collected from patients with gastric cardia adenocarcinoma and normal tissue was collected from healthy controls. RKIP expression was detected in these tissues and the serum levels of NF-κB p65 and T-lymphocyte subsets were measured. Positive RKIP expression was higher in gastric cardia adenocarcinoma tissues than in precancerous tissues. The serum level of total NF-κB p65 was higher in patients with gastric cardia adenocarcinoma than in healthy controls. Levels of NF-κB p65 did not correlate with positive and negative expression of RKIP, but were higher in patients with lymph node metastasis than in those without it. The cellular immune function of the gastric cardia adenocarcinoma group was lower than in normal controls, particularly in cases with negative RKIP expression. RKIP is downregulated in gastric cardia adenocarcinoma tissues, which is related to the occurrence, progression, invasion, and metastasis of tumors. The possible mechanism for this may be the inhibition of NF-κB activity and cellular immune function, which allows for the escape of tumor cells from immune surveillance.