Background/Aim: Successful conception and pregnancy require a complex and organized communication between the embryo (allograft) and the mother’s (host) immune system. The decidual NK cells (dNK), among other leukocyte subsets, have an important role in orchestrating this immune environment. This study aimed to investigate how exposure to benign and malignant trophoblastic cell lines affects the phenotype and cytotoxic function of dNK cells. Materials and Methods: In our study, we isolated dNK cells from term, healthy human placentas and sorted them to achieve a pure, CD56 bright, CD16 negative population. These NK cells were co-cultured with HTR-8 (benign) and Jeg-3 (malignant) trophoblastic cell lines for one and five days. The NK cells were isolated again after the exposure to the trophoblastic cells, and their phenotype was assessed again. Their cytotoxicity was also measured and compared to the cytotoxicity of dNK cells not exposed to trophoblastic cells. Results: After one day of co-culture, dNK phenotype remained unchanged with both cell lines. However, a five-day exposure to Jeg-3 cells resulted in a shift toward a CD56 diminished CD16+ phenotype, resembling peripheral NK cells. Additionally, cytotoxic activity of dNK cells was significantly reduced after co-culture with both cell lines, with a more pronounced suppression observed following exposure to Jeg-3 cells. Conclusion: There are certain similarities between the immune evasion of tumor cells and the physiological invasion of the trophoblastic cells of embryonic origin into the maternal decidua. Understanding the ways of interaction between dNK cells and the trophoblastic cells may reveal similar immunological interactions between the host’s NK cells and tumor cells.