Abstract： Objective To investigate the efficacy and safety of serum HE4,CEA,CYFRA21-1,NSE and SCC levels for assessing chemotherapy and targeted drug use in lung cancer.Methods Retrospective analysis of 106 patients with advanced lung cancer admitted to Tangshan People's Hospital from March 2020 to December 2022 were used as study subjects,and they were divided into chemotherapy group(n=56)and targeted thera-py group(n=50)according to the treatment modality.The chemotherapy group was given pemetrexed com-bined with cisplatin chemotherapy,and the targeted therapy group was given gefitinib orally,and the patients were shown to be positive for epidermal growth factor gene mutation.The clinical efficacy,serum HE4,CEA,CYFRA21-1,NSE and SCC levels before and after treatment,and the occurrence of adverse effects were ob-served and compared between the two groups.Results The total efficiency of treatment in the targeted thera-py group was higher than that in the traditional chemotherapy group,and the difference was statistically sig-nificant(P＜0.05);after treatment,the serum HE4,CEA,CYFRA21-1,NSE and SCC levels in the targeted therapy group were lower than those in the traditional chemotherapy group,and the difference was statistically significant(P＜0.05);the incidence of blood routine and liver and kidney function abnormalities in the targe-ted therapy group were lower than those in the chemotherapy group,and the difference was The incidence of blood routine and liver and kidney function abnormalities in the targeted therapy group were lower than those in the chemotherapy group,and the difference was statistically significant(P＜0.05),while the incidence of rash,diarrhea,decreased appetite and arthralgia adverse reactions were lower in the targeted therapy group than in the chemotherapy group,but the difference between the two groups was not statistically significant(P＞0.05).Conclusion The efficacy of targeted drug use is remarkable,and it can reduce serum HE4,CEA,CYFRA21-1,NSE and SCC levels with few adverse effects and high safety.