Objective To investigate the efficacy of cisplatin and pemetrexed combined with recombinant human endostatin injection in the treatment of elderly lung adenocarcinoma，and its effect on the expression levels of circulating tumor cells（CTC），epithelial cell transformation sequence 2（ECT2）and cyclooxygenase⁃2（COX⁃2）. Methods 102 elderly patients with lung adenocarcinoma had been hospitalized between March 2019 and March 2022 were selected as the study subjects. They were divided into two groups（a control group and an observation group，51 for each group）according to the random number table method. The control group was treated with con⁃ ventional cisplatin plus pemetrexed，while the observation group received recombinant human endostatin injection in addition to cisplatin and pemetrexed. Circulating tumor cells（CTC），epithelial cell transformation sequence 2 （ECT2），cyclooxygenase ⁃2（COX ⁃2），vascular endothelial growth factor（VEGF），matrix metalloproteinase ⁃9 （MMP⁃9），programmed death ligand 1（PD⁃L1），toxic and adverse reactions，and short⁃term efficacy were com⁃ pared between the two groups. Results After treatment，the detection values of CTC，ECT2，COX ⁃2，VEGF， MMP⁃9 and PD⁃L1 were lower in the observation group than in the control group，and the differences were statisti⁃ cally significant（t = 28.255，4.896，18.811，34.134，12.524，15.614，P < 0.05）. There was no significant difference in the total incidence of toxic and adverse reactions between the two groups（χ2 = 1.253，P > 0.05）. The RR and DCR were higher in the observation group than in the control group，and the differences were statistically signifi⁃ cant（χ2 = 11.429，7.809，P < 0.05）. Conclusion The combination therapy with cisplatin，pemetrexed and recombinant human endostatin injection can further reduce the expression levels of CTC，ECT2 and COX⁃2 in elderly patients with lung adenocarcinoma，which has a positive impact on improving the effect of disease control and short⁃term efficacy. The safety of medications is higher，which is worthy of promotion and application.