Objective To evaluate the diagnostic value of seven autoantibodies in the differential diagnosis of lung cancer patients. Methods The serum levels of seven autoantibodies p53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGEA1 and CAGE were detected by ELISA in 122 subjects, which include 65 extrapulmonary tumors, 20 benign lung diseases, 3 small cell lung cancers, 20 physical examination subjects and 14 non-small cell lung cancers. Subsequently, the results were statistically analyzed by SPSS. Results The subjects were divided into five sub-groups, included extrapulmonary tumors, benign pulmonary lesions, small cell lung cancer, physical examination and non-small cell lung cancer subgroup. p53, SOX2, GBU4-5 and MAGEA1 in small cell cancer subgroup had significantly higher expression levels. Subjects were categorized differently using a ROC curve for statistical analy-sis. The results showed that p53 (AUC=0.664, P＜0.05) was significantly higher in lung cancer group than an-other group. GBU4-5 (AUC=0.639, P＜0.05) and the combination of the seven indicators (AUC=0.635,P＜0.05) had a certain diagnostic value for differential diagnosis of the non-malignant tumor group and the tumor group. MAGEA1, CAGE, PGP9.5, SOX2 and the combination of the seven indexes(AUC＞0.8,P＜0.05)had a high value in the differential diagnosis of small cell lung cancer group and another group. MAGEA1 ( AUC =0.333,P＜0.05) had some value in the differential diagnosis of the physical examination group and another group. p53 (AUC=0.33), PGP9.5 (AUC=0.355), GBU4-5(AUC=0.280),CAGE(AUC=0.341) and seven indi-cators combined detection( AUC =0.731 ) had certain value in the differential diagnosis of benign lung diseases group and another group. Conclusion According to the different groups, the detection of seven autoantibodies and their combined detection have a certain value for differential diagnosis of lung cancer.