Abstract： Objective To investigate the diagnostic value of human epididymal protein 4(HE4)and Interleu-kin 6(IL-6)in non-small cell lung cancer(NSCLC).Methods Fifty NSCLC patients who were hospitalized at Hebei Provincial People's Hospital from January 2020 to December 2022 were selected as the lung cancer group,fifty healthy individuals in the same period as the control group retrospective analysis was performed.Serum HE4 and IL-6 levels were measured using electrochemical luminescence method,and the basic charac-teristics and differences in HE4 and IL-6 levels between the two groups were analyzed and compared.Logistic regression analysis was used to screen effective indicators for diagnosing NSCLC,and a predictive model for diagnosing NSCLC was constructed.The diagnostic value of serum HE4 and IL-6 in NSCLC was analyzed by Receiver operating characteristic.Results The serum HE4 level in the lung cancer group[(198.12±66.42)pmol/L]was higher than that in the control group[(79.56±15.77)pmol/L],and the serum IL-6 level in the lung cancer group[(16.45±8.96)pg/ml]was higher than that in the control group[(4.96±1.91)pg/ml],with a statistically significant difference(P＜0.05).There was no statistically significant difference in age and gen-der distribution between the two groups(P＞0.05).Comparing the expression levels of serum HE4 and IL-6 with different clinical characteristics,it was concluded that there was no statistically significant difference in expression levels of serum HE4 and IL-6 with age,gender,and pathological type in NSCLC patients(P＞0.05).The serum HE4 and IL-6 levels in Ⅲ-Ⅳ patients were higher than those in Ⅰ-Ⅱ(t=-2.440,P＜0.018;t=-2.889,P＜0.006),and serum HE4 and IL-6 levels in patients without distant metastasis were significantly lower than those in patients with distant metastasis(t=2.455,P＜0.018;t=2.040,P＜0.047),with a statistically significant difference.Assuming the independent variables X1=HE4 and X2=IL-6,a bina-ry logistic regression analysis was performed with pathological diagnosis results as the dependent variable.The probability prediction regression model for lung cancer was obtained as Logit(P)=0.084X1+0.538X2-13.299,with a prediction accuracy of 98.0％.There is a close relationship between the average levels of serum HE4 and IL-6 water and the occurrence of NSCLC.Receiver operating characteristic analysis showed that di-agnostic threshold of serum HE4 for NSCLC was ≥110.73pmol/L,and the area under the curve(AUC)was 0.948(95％CI:0.896～0.998).Using a cut-off point of 110.73pmol/L,the sensitivity and specificity of HE4 were 90.0％and 98.0％,respectively.The diagnostic threshold of serum IL-6 for NSCLC is ≥7.16pg/ml,and the area under the curve(AUC)is 0.869(95％CI:0.784～0.954).Using a cut-off point of 7.16pg/ml,the sensitivity and specificity of IL-6 were 84.0％and 92.0％,respectively.The sensitivity and specificity of the combined detection of serum HE4 and IL-6 in the diagnosis of NSCLC were 98.0％and 96.0％,respectively.Conclusion Serum HE4 and IL-6 have certain value in the diagnosis of NSCLC.The prediction model estab-lished through HE4 and IL-6 serum tumor markers has good value in early prediction of NSCLC.