Objective To compare the efficacy and safety of anlotinib(AL)and bevacizumab(BEVA)in the treatment of advanced lung adenocarcinoma(LUAD)with acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKI).Methods The clinical data of patients with EGFR-TKI-resistant LUAD who were treated in the Department of Oncology of Yibin Third People's Hospital from January 2022 to January 2023 were retrospectively analyzed.According to the treatment plan,patients were divided into BEVA group and AL group.Both groups were treated with BEVA injection or AL capsule in combination with standard chemotherapy for a total of 4 cycles.The main outcome measures included changes in tumor marker levels[carcinoembryonic antigen(CEA),neuron-specific enolase(NSE),and vascular endothelial growth factor(VEGF)],recent clinical efficacy[overall response rate(ORR)and disease control rate(DCR)],progression-free survival(PFS),1-year survival rate,and drug-related adverse reactions.Results A total of 60 patients with EGFR-TKI-resistant LUAD were included in the study,including 32 patients in the BEVA group and 28 patients in the AL group.After four cycles of treatment,the levels of serum CEA,NSE,and VEGF in both groups significantly decreased,and AL group was lower than BEVA group(P<0.05).There were no significant statistical differences in the complete remission rate,partial remission rate,disease stability rate,and ORR between the two groups(P>0.05).Compared with the BEVA group,the AL group had a lower rate of disease progression(P<0.05)and a higher DCR(P<0.05).In addition,the median PFS in the BEVA group was significantly longer than that in the AL group(8.4 vs.7.2 months,P<0.05),while there was no significant difference in survival rate between the two groups(P>0.05).In terms of adverse reactions,patients in the AL group had a lower incidence of nausea and vomiting,but a higher incidence of bone marrow suppression,resulting in a lower overall adverse reaction grade.Conclusion Compared with the BEVA combination chemotherapy regimen,AL combination chemotherapy showed better efficacy and good safety in the treatment of EGFR-TKI-resistant advanced LUAD.