Abstract: In recent years, many studies have demonstrated the potential of immune checkpoint inhibitors in the treatment of multiple types of cancers. Natural killer (NK) cells are an important part of the innate immune system and play an essential role in tumor immune surveillance. Their effects depend on their binding to inhibitory receptors, activating receptors, or both and the fact that they do not require major histocompatibility complex molecules to kill tumor cells. NK cells have shown great potential against both solid and hematologic tumors and have been increasingly identified as a promising therapeutic target for cancer immunotherapy. Some newly emerging checkpoint receptors and molecules have been revealed to mediate NK cell dysfunction in the tumor microenvironment, making them ideal targets for tumor immunotherapy. Thus, this paper will focus on the roles of these newly emerging immune checkpoint receptors in the regulation of NK cells and their potential application in tumor immunotherapy.