Objective To observe the clinical efficacy of Fuzheng Quxie Formula (扶正祛邪方) combined with EGFR-TKI in the treatment of advanced lung adenocarcinoma, and to explore the integrated traditional Chinese and Western medicine diagnosis and treatment of advanced non-small cell lung cancer.Methods A total of 448 patients with advanced lung adenocarcinoma were enrolled in this prospective cohort study. Among them, the patients from Shanghai Traditional Chinese Medicine Hospital were selected as the observation group (Fuzheng Quxie Formula +EGFR-TKI group), and the patients from Shanghai Chest Hospital were selected as the control group (EGFR-TKI group). The clinical efficacy, progression-free survival (PFS), safety and quality of life of the two groups were observed.Results The median PFS of Fuzheng Quxie Formula +EGFR-TKI group was longer than that of EGFR-TKI group (14.2 months vs. 10.43 months) (P<0.05). Fuzheng Quxie Formula combined with EGFR-TKI significantly prolonged the median PFS of patients in the EGFR-TKI first-line treatment subgroup, exon 19 deletion subgroup, exon 21 mutation subgroup and gefitinib treatment subgroup (P<0.05). However, no significant benefit was found in patients in the second-line treatment subgroup, the erlotinib treatment subgroup and the icotinib treatment subgroup (P>0.05). Univariate analysis showed that Fuzheng Quxie Formula, gender, age, smoking history, and chemotherapy were associated with PFS (P<0.05). Multivariate regression analysis showed that Fuzheng Quxie Formula was an independent protective factor for PFS in patients with EGFR mutations in advanced stage (P<0.05), while smoking was a risk factor for PFS (P<0.05).Conclusion Fuzheng Quxie Formula combined with EGFR-TKI treatment can prolong the progression-free survival of patients with advanced lung adenocarcinoma, and delay the drug resistance of TKI.