Objective To explore the changes in levels of serum exosomes miR-152-5p and AGAP2-AS1 in non-small cell lung cancer (NSCLC) and their evaluation value for prognosis.Methods The clinical data of 120 NSCLC patients who were admitted to the hospital from June 2014 to December 2016 were collected. Another 60 healthy people who underwent physical examination in the hospital during the same period were enrolled as control group. Serum exosomes were isolated and identified. The expression levels of miR-152-5p and lncRNA AGAP2-AS1 were detected by RT-PCR. The changes in levels of serum exosomes miR-152-5p and lncRNA AGAP2-AS1 were analyzed. And their relationship with clinicopathology was explored. According to the prognosis after 3 years of follow-up, patients were divided into survival group and death group. The value of serum exosomes miR-152-5p and lncRNA AGAP2-AS1 in diagnosis of NSCLC and evaluation of prognosis was analyzed. Results The expression level of miR-152-5p in NSCLC group was lower than that in control group, while expression level of lncRNA AGAP2-AS1 was higher than that in control group (P＜0.05). The area under the ROC curve (AUC) of miR-152-5p combined with lncRNA AGAP2-AS1 for diagnosis of NSCLC was 0.902, greater than that of miR-152-5p and lncRNA AGAP2-AS1 alone (0.813, 0.808) (P＜0.05). There were no significant differences in the expression levels of miR-152-5p and lncRNA AGAP2-AS1 among NSCLC patients with different genders and age (P＞0.05). The expression level of miR-152-5p in patients with clinical staging at stage Ⅲ~Ⅳ, local invasion of T3~T4 and lymph node metastasis was lower than that with clinical staging at stage Ⅰ~Ⅱ, local invasion of T1~T2 and without lymph node metastasis, while expression level of lncRNA AGAP2-AS1 was higher than that in these kinds of patients (P＜0.05). AUC of miR-152-5p combined with lncRNA AGAP2-AS1 for determining stage Ⅰ~Ⅱ and Ⅲ~Ⅳ was 0.902, higher than that of them alone (0.802, 0.815) (P＜0.05). After 3 years of follow-up, there were 5 cases lost to follow-up among the 120 NSCLC patients. Among the remaining 115 patients, there were 66 cases in survival group and 49 cases in death group. The expression level of miR-152-5p in survival group was higher than that in death group, while expression level of lncRNA AGAP2-AS1 was lower than that in death group (P＜0.05). AUC of miR-152-5p combined with lncRNA AGAP2-AS1 for determining prognosis was 0.849, greater than that of miR-152-5p and lncRNA AGAP2-AS1 alone (0.739, 0.714) (P＜0.05). Conclusion Serum exosome miR-152-5p is lowly expressed, while lncRNA AGAP2-AS1 is highly expressed in NSCLC patients. Their expression levels are related to clinical stages of NSCLC, tumor infiltration and lymph node metastasis, which are of important value in disease diagnosis and prognosis assessment.