Lung cancer is the leading cause of cancer death in most countries. Although early diagnosis and treatment critically influence prognosis, lung cancers are generally only discovered in the late stages of the disease .Widely-used screening and diagnostic methods are not suitable for preventive screening, and high-throughput technologies based on serum biomarkers are needed. The aim of the study was to evaluate the clinical diagnostic value of combined detection of serum CEA, CYFRA21-1, CRP, and prolactin Gene in lung cancer. The study involved a total of 274 participants, divided into three distinct groups: 123 lung cancer patients, 52 patients with benign lung disease, and 99 healthy controls. These participants were selected based on predefined inclusion and exclusion criteria.5 ml of venous blood samples were taken from all participants and it was collected in a test tube containing anticoagulant and then centrifuged at 3000 rpm for 10 minutes. Serum was separated and used to measure the amount of CEA, CYFRA21-1, CRP, and prolactin Gene using ELISA method. The results showed that the serum levels of CEA, CYFRA21-1, CRP, and prolactin in the malignant group were significantly higher than those in the benign and healthy groups (P0.05), and CYFRA21-1 in non-small cell carcinoma was significantly higher than that in small cell carcinoma (P0.05). However, there were significant differences in the levels of CEA and prolactin in different TMN stages (P0.05). A panel of CEA, CYFRA21-1, CRP, and prolactin Gene was found as promising serum biomarkers for the diagnosis of LC with relatively high sensitivity and specificity. CEA, CYFRA21-1, CRP, and prolactin Gene combined biomarker panel holds potential for rapid screening and improving the diagnosis of early-stage LC, thus potentially alsoimproving its prognosis.