To detect the expression of CCL5 in tissue and serum of patients with NSCLC and explore the clinical significance of expression of CCL5. Methods Cancer tissues, adjacent tissues and clinical data of 72 patients with NSCLC who were diagnosed for the first time and underwent surgical treatment in Suqian Hospital of Xuzhou Medical University were collected. Immunohistochemistry was used to detect the expression of CCL5 in cancer and adjacent tissues. Realtime PCR was used to detect the expression of CCL5mRNA in serum of NSCLC and healthy controls. The correlation between CCL5 expression and clinical and pathological features of patients and its influence on prognosis were analyzed. The lung adenocarcinoma A549 cells, siRNA CCL5 transfection cells were cultivated In vitro. The changes of cell proliferation, migration and invasion after down-regulating CCL5 expression were observed. Results The expression of CCL5 in tissue and serum of NSCLC patients was high, CCL5 expression was correlated with the degree of NSCLC differentiation and TNM stage (P=0.019, P=0.033). The K-M analysis results showed that the upregulation of CCL5 expression was significantly correlated with the decrease of overall survival rate. Silencing CCL5 expression can inhibit the proliferation and invasion of lung adenocarcinoma. Conclusion CCL5 expression is elevated in NSCLC and may contribute to the invasion and metastasis of lung cancer, suggesting that CCL5 might be a prognostic factor in lung adenocarcinoma.