Abstract: Objective To investigate the value of combined detection of serum carcino-embryonic antigen(CEA), cytokeratin 19 fragment antigen 21-1(CYFRA21-1)and carbohydrate antigen 125(CA125)in non-small cell lung cancer(NSCLC). Methods A total of 45 patients with NSCLC were selected as observation group, and 40 patients with benign pulmonary lesions during the same period were selected as control group. The levels of CEA, CYFRA21-1 and CA125 of all patients were detected. The specificity, sensitivity, accuracy of single and combined detection were analyzed. Results The levels of CEA, CYFRA21-1 and CA125 in the observation group were higher than those in the control group, and the differences were statistically significant(P<0.05). Compared with single detection of CEA, CYFRA21-1 or CA125, the positive detection rate of combined detection was higher, and the difference was statistically significant(P<0.05). The specificity, sensitivity and accuracy of combined detection were higher than those of single detection. Conclusion Combined detection of serum CEA, CYFRA21-1 and CA125 in NSCLC has higher diagnostic value, which can provide a reliable basis for the clinical diagnosis and prognostic judgement.