In this study, SMYD2 was found to be upregulated, and patients with higher SMYD2 expression showed a poor prognosis among our cohort of 186 ccRCC cases diagnosed across three medical centers in China; our results also showed that SMYD2 appears to play an oncogenic role in RCC, particularly in ccRCC. Here, SMYD2 is linked to nonpapillary renal cell carcinoma.