Objectives: To analyze and study the efficacy and safety of Endu combined with pemetrexed and cisplatin in the clinical treatment of lung adenocarcinoma. Methods: From August 2016 to September 2020, 32 patients with lung adenocarcinoma who were treated in our hospital were selected for group trials. According to their specific treatment plan, the patients were divided into control group and experimental group, with 16 cases in each group. The control group was treated with pemetrexed and cisplatin, and the experimental group was treated with Endostar combined with the treatment received by the control group. The clinical efficacy and safety of the two regimens were assessed by comparing the changes in symptoms and the incidence of adverse reactions between the two groups of patients after treatment. Results: The disease control rate of the experimental group was significantly higher than that of the control group, and there was no significant difference in the incidence of adverse reactions between the two groups. Conclusions: From the experimental results, we found that the treatment of patients with lung adenocarcinoma by Endostar combined with pemetrexed and cisplatin can effectively improve the treatment efficacy without increasing adverse reactions and therefore relevant chemotherapy regimens can be considered for wider clinical applications.