Abstract: Kidney transplant recipient (KTR) faces significant challenges in long-term survival, with the incidence of post-transplant malignancies being 2 to 3 times higher than that of the general population, making it the second leading cause of death in KTR. Immune checkpoint inhibitors (ICI) represent an important breakthrough in malignancy treatment, significantly improving the prognosis of some malignancy patients by blocking co-inhibitory signaling molecules and activating T lymphocyte activity. However, due to concerns about the risk of rejection, solid organ transplant recipients, including KTR, are usually excluded from ICI clinical trials. Existing evidence shows that the incidence of rejection during ICI treatment can be as high as 40%-50%, with the specific mechanisms not yet clear. Therefore, how to enable KTR to effectively benefit from the anti-tumor effects of ICI while avoiding rejection is crucial. This article focuses on the core contradiction of ICI in the treatment of post-transplant malignancies in KTR, that is, the dual effects of activating anti-tumor immunity and inducing transplant kidney rejection. It systematically reviews the current clinical application status and challenges, and explores optimization strategies for the delicate balance between restoring anti-tumor immunity and triggering rejection.