Earthworm's celomic fluid has long attracted scientists' interest due to its toxic properties. It has been shown that subjecting it to a short heating at 70 ° C, which effectively reduces the toxicity to healthy cells, and demonstrates the selective action of the obtained Venetin-1 preparation against Candida albicans cells, as well as tumor cells from the A549 line. In order to find out about the molecular mechanisms behind the anti-cancer properties of the preparation, the conducted research investigated the proteome response of A549 cells to the presence of Venetin-1. The sequential window acquisition of all theoretical mass spectra (SWATH-MS) methodology was used for the analysis, which allows for a relative quantitative analysis to be carried out without radiolabelling. The results showed that the formulation did not induce significant proteome responses in healthy BEAS cells. In the case of the tumor line, 31 proteins were up-regulated and 18 proteins down-regulated. Proteins with increased expression in neoplastic cells are mainly associated with the mitochondrion, membrane transport and the endoplasmic reticulum. In the case of altered proteins, Venetin-1 interferes in proteins that stabilize the structures, i.e. keratin, glycolysis / gluconeogenesis and metabolic processes. This information shows the potential of Venetin-1, which may be used in the treatment of lung cancer in the future.