Renal transplantation is currently the best treatment option for patients with end-stage kidney disease. Ischemia/reperfusion injury (IRI), which is an inevitable event during renal transplantation, has a profound impact on the function of transplanted kidneys. It has been well demonstrated that innate immune system plays an important role in the process of renal IRI. As a critical component of innate immune system, Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome has received great attention from scientific community over the past decade. The main function of NLRP3 inflammasome is mediating activation of caspase-1 and maturation of interleukin (IL)-1β and IL-18. In this review, we summarize the associated molecular signaling events about NLRP3 inflammasome in renal IRI, and highlight the possibility of targeting NLRP3 inflammasome to minimize renal IRI during transplantation.