Damage-associated molecular pattern (DAMP) molecules can initiate an immune response through Toll-like receptors (TLRs). DAMPs are released from cells as a response to the extracellular danger and can be by-products of tissue damage. In cancer microenvironment necrotic cells release debris which has potency to become DAMPs. Non-small cell lung cancer (NSCLC) is often accompanied by pleural effusion (PE), which contains a variety of DAMPs. Surfactant protein A (SP-A) and heat shock protein 70 (Hsp70) are important DAMPs in the respiratory tract. The aim of this study was to determine a correlation between SP-A or Hsp70 and development of PE in the course of NSCLC. Moreover, we aimed to determine relationships between DAMPs and certain humoral factors associated with formation and persistence of PE as well as pleural-residing macrophages. In 34 PE samples, we estimated concentration of SP-A, Hsp70, IL-6, IL-18, G-CSF, M-CSF, SCF, SDF1α, VEGF as well as the fraction of macrophages and their pattern of polarization. We have found correlations between the concentration of the SP-A and Hsp70 and the percentage of PE-derived macrophages, also between concentrations of SP-A and Hsp70, and cytokines which participate in inflammation and processes involved in remodeling of extracellular matrix (ECM). Our data indicate an important role of SP-A during the development of PE associated with NSCLC. We suggest that measurement of concentration level of SP-A can be helpful in the course of diagnosis of malignant PE associated with NSCLC.Keywords: Hsp70; M1 vs M2; Non-small cell lung cancer; Pleural effusions; Pleural macrophages; SP-A.