In this study, the application of AZ505 or conditional knockdown of Smyd2 in renal tubular epithelial cells ameliorated cisplatin‐induced renal injury and alleviated renal tubular epithelial cell apoptosis in cisplatin‐induced CKD mice, which may be related to the inhibition of the NF‐κB signaling pathway. Here, SMYD2 is linked to chronic kidney disease.