Background: Cyclophilin A (CypA), which is a protein that mediates protein folding and trafficking, has known to be associated with cancer progression and drug resistance such as cisplatin. However, the actual effect in cancer patients has not been elucidated. Methods: We collected clinical data from the cohort of 289 gastric cancer patients. Subjects were selected as following criteria: 1) adjuvant or first-line palliative chemotherapy containing platinum, 2) available FFPE tissue for immunohistochemical stain for CypA. We divided the population into two groups; Group A was patients who received adjuvant chemotherapy and Group P was those of palliative chemotherapy-treated group. The score of CypA immunohistochemistry was calculated depending on the intensity of stain and the percentage of stained cells. We performed survival analysis based on CypA expression. Results: 1) Group A (N = 147) Patients with lower expression of CypA ( < vs. ≥ median IHC score) showed significantly worse progression-free survival (PFS, 2.4 years vs NR, p = 0.043), and overall survival (OS, 3.4 months vs. NR, p = 0.002). In subgroup analysis, level of CypA expression discriminated PFS significantly in patients with age less than 65, poorly differentiated histology, signet ring cell type, and OS for those with use of oxaliplatin, age less than 65, stage III, poorly differentiated histology, diffuse type of Lauren classification, and signet ring cell type favoring higher expression of CypA. 2) Group P (N = 142) There was no relationship between expression level of CypA and PFS/OS in patients with palliative settings. However, in patients who were treated with oxaliplatin-containing chemotherapy, lower expression of CypA showed worse OS (8.3 vs 11.1 months, p = 0.003) Conclusions: Lower level of CypA expression was associated with worse PFS and OS in patients with adjuvant setting, especially in case of advanced stage, and high grade histology. Although CypA did not have significant effect on survivals in palliative chemotherapy-received patients, those who received oxaliplatin showed worse OS with lower CypA.