Abstract: The detection of serum biomarkers for lung cancer is a noninvasive procedure, with important value in the diagnosis, therapeutic effect monitoring, and prognosis evaluation of lung cancer. Numerous clinical studies have reported limited diagnostic efficacy of detection using a single lung cancer serum biomarker but that combinatory detection improved the diagnostic performance of the markers and was highly correlated with histotype. Among the biomarkers, cytokeratin fragment 19 (CYFRA21-1), carcinoembryonic antigen (CEA), and squamous cell carcinoma antigen (SCC-Ag) showed higher sensitivity and specificity for non-small cell lung cancer (NSCLC), while neuron-specific enolase (NSE) and pro-gastrin-releasing peptide (ProGRP) showed preferential sensitivity and specificity for small cell lung cancer (SCLC). Although human epididymis protein 4 (HE4) lacks histotype specificity, its use can improve the detection sensitivity of SCLC and lung adenocarcinoma when combined with other markers. Combinatory examination of serum biomarkers of lung cancer with low-dose computed tomography can further improve the detection rate. A reference interval is an indispensable parameter for the clinical application of tumor markers, and its standardization is important for ensuring its reliability. This consensus expounds the clinical application of serum biomarkers of lung cancer, including the combined detection method, result interpretation, and establishment of reference intervals of serum biomarkers.