〔Abstract〕 Objective To investigate the correlation between co-signaling molecule B7-H3 and epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI) target therapy in acquired drug resistance of lung adenocarcinoma. Methods Immunohistochemical method was used to detect B7-H3 expression in 56 lung adenocarcinoma patients, and the cohort was divided into low and high B7-H3 expression groups.The proportion and occurrence time of acquired drug resistance after EGFR-TKI targeted therapy were compared between the two groups.Gefitinib-resistant EGFR mutant lung adenocarcinoma cell lines H3255 and HCC827 were induced and cultured in vitro.The wild-type cell lines were used as control, and the expression level of B7-H3 on resistant cell lines B7-H3 was analyzed by flow cytometry. Results In 56 lung adenocarcinoma patients, 31 cases and 25 cases had low and high B7-H3 expression, respectively.By the end of this study, the cases of acquired drug resistance in patients with low and high B7-H3 expression were 12 cases(38.7%) and 14 cases(56.0%)(P=0.19,χ2=1.663),and the median drug resistance time was 13.2 months and 5.1 months(P=0.004,t=3.193),respectively.Compared with wild-type H3255 and HCC827 cell lines, the expression level of drug-resistant strain B7-H3 further increased. Conclusion B7-H3 expression level is correlated with acquired drug resistance of EGFR-TKI targeted therapy in lung adenocarcinoma.