Adaptive immune cells play an important role in mounting antigen-specific anti-tumor immunity. The contribution of innate immune cells such as monocytes, macrophages, natural killer (NK) cells, dendritic cells, and gamma-delta T cells is well-studied in cancer immunology. NK are innate lymphoid cells that show effector and regulatory function in a contact-dependent and contact-independent manner. The cytotoxic function of NK cells plays an important role in killing the infected and transformed host cells and controlling infection and tumor growth. However, several studies have also ascribed the role of NK cells in inducing pathophysiology in autoimmune diseases, promoting immune tolerance in the uterus, and anti-tumor function in the tumor microenvironment. We discussed the fundamentals of NK cell biology, its distribution in different organs, cellular and molecular interactions, and its cytotoxic and non-cytotoxic functions in cancer biology. We also highlighted the use of NK cell-based adoptive cellular therapy in cancer.