The aim of the study was to investigate the application value of neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR) in the prediction of chemotherapy response and prognosis in patients with advanced gastric cancer. In total, 120 patients with unresectable gastric cancer were included and separated into two groups according to the median values of NLR or PLR (NLR low: <4.62 or NLR high: ≥4.62 and PLR low: <235 or PLR high: ≥235, respectively). Low baseline NLR level correlated with improved clinicopathological characteristics, including smaller tumor size, well differentiation and less metastasis. Low baseline PLR level also associated with less metastasis. Patients with a low baseline level of NLR or PLR had an improved response to chemotherapy. Patients with a higher baseline NLR and PLR had decreased progression-free survival (PFS) and overall survival (OS) ratios. Alterations in the NLR and PLR levels were associated with therapeutic efficacy and prognosis. The patients who remained in or switched to the low NLR level subgroup subsequent to first-line chemotherapy had an improved response and improved OS ratios, compared to the patients remaining in or switching to the high NLR level group. Similar results were observed when the PLR level was investigated. In conclusion, baseline NLR and PLR measurements, as well as changes of NLR and PLR following chemotherapy can predict the prognostic results in patients with unresectable gastric cancer.