We explored the possible mechanisms by which SMYD2 regulates cisplatin‐induced apoptosis in renal tubular epithelial cells and verified that SMYD2 and its non‐histone substrate, NF‐κB p65, have an interaction, suggesting that SMYD2 may promote the process of CKD by activating NF‐κB‐mediated apoptosis. Here, SMYD2 is linked to chronic kidney disease.