Lung cancer has consistently ranked first as the cause of cancer-associated mortality. The 5-year survival rate has risen slowly, and the main obstacle to improving the prognosis of patients has been that lung cancer is usually diagnosed at an advanced or incurable stage. Thus, early detection and timely intervention are the most effective ways to reduce lung cancer mortality. Tumor-specific molecules and cellular elements are abundant in circulation, providing real-time information in a noninvasive and cost-effective manner during lung cancer development. These circulating biomarkers are emerging as promising tools for early detection of lung cancer and can be used to supplement computed tomography screening, as well as for prognosis prediction and treatment response monitoring. Serum and plasma are the main sources of circulating biomarkers, and protein biomarkers have been most extensively studied. In this review, we summarize the research progress on three most common types of blood protein biomarkers (tumor-associated antigens, autoantibodies, and exosomal proteins) in lung cancer. This review will potentially guide researchers toward a more comprehensive understanding of candidate lung cancer protein biomarkers in the blood to facilitate their translation to the clinic.Copyright © 2022. Published by Elsevier B.V.