Objective To investigate the effects of endostatin combined with icotinib on chemotherapy sensitivity,tumor markers,and prognosis in patients with advanced non-small cell lung cancer(NSCLC).Methods A total of 88 patients with advanced NSCLC admitted to our hospital from January 2019 to August 2020 were selected and randomly assigned to two groups,with 44 patients in each group.The patients in both groups were treated with pemetrexed+cisplatin(PP)chemotherapy,whereas those in the control group were administered echitinib and those in the observation group was treated with endostatin combined with icotinib.Patients in the two groups were assessed for clinical efficacy,tumor markers[carbohydrate antigen(CA)50,carcinoembryonic antigen(CEA),cytokeratin 19 fragment(CYFRA)21-1],T lymphocyte subsets,microRNA expression levels(miR-34b,miR-204-5p,and miR-158-5p)and tyrosine protein excitation.We also examined janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathways,along with adverse reactions.Results We detected no significant differences between the two groups with respect the total response rate(P>0.05).Following treatment,the levels of serum CA50,CEA,and CYFRA21-1 in the observation group patients were found to be lower than those of patients in the control group(P<0.05).Similarly,the levels of CD3+,CD4+,CD4+/CD8+in observation group patients were higher than those in the control group patients,whereas the levels of CD8+were lower than those in the control patients(P<0.05).Furthermore,the expression levels of miR-34b,miR-204-5p,and miR-158-5p in the observation group patients were higher than those in the control group patients,whereas contrastingly,the levels of J AK2 and STAT3 mRNA expression were lower than those in the control group(P<0.05).In addition,the progression-free survival of the observation group patients was higher than that of control group patients(P<0.05).Conclusion The combination of endostatin and icotinib has clear therapeutic efficacy in patients with advanced NSCLC,which can con-tribute to enhancing their sensitivity to chemotherapy and immune function.We speculate that the underlying mechanisms of action may be associated with a reduction in the activity of the JAK2/STAT3 signaling pathway,which is beneficial for patient prognosis.