Objective To investigate the value of peripheral blood neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in evaluating chemotherapy response and prognosis of patients with non-small cell lung cancer (NSCLC). Methods The data of 87 patients with NSCLC admitted to the hospital from March 2019 to June 2021 were retrospectively analyzed. Peripheral blood neutrophils, lymphocytes, and platelets were measured before chemotherapy to calculate NLR and PLR. The efficacy and prognosis were evaluated. The value of NLR and PLR in evaluating chemotherapy response and the prognosis was analyzed. Results NLR and PLR were related to smoking history, tumor stage, and lymph node metastasis (P<0.05). The effective rate was 71.26% after 2 cycles of chemotherapy, and NLR and PLR in the effective group were significantly lower than those in the ineffective group (P<0.05). The receiver operating characteristic curve showed that the areas under the curve of NLR, PLR alone and in combination to evaluate chemotherapy response were 0.859, 0.785, and 0.926, respectively. The incidence of poor prognosis was 32.18%. Univariate analysis and multivariate logistic regression analysis showed that differentiation degree, PLR and NLR were related to the prognosis (P<0.05). Conclusion Peripheral blood NLR and PLR are related to many clinical characteristics of patients with NSCLC. The two can be used to evaluate chemotherapy response and the prognosis.