〔Abstract〕 Objective To explore the expression of histone methyltransferase(SETD2) in clear cell renal cell carcinoma(ccRCC) and the influence on prognosis of patients, and to study the possible regulatory mechanism of it. Methods Gene mutation data, transcriptome data and clinical data of patients with ccRCC were downloaded from cancer genome project database(TCGA), and the R software V 4.0.3 was used for statistical analysis of gene expression differences. Kaplan-Meier plotter was used to study the different prognosis of patients with different SETD2 expression and immune infiltration conditions and to reveal the potential mechanism by which SETD2 mutation regulated the progression of ccRCC,meanwhile clinical data were used for verification. Results TIMER2 analysis showed that the expression of SETD2 was significantly down-regulated in ccRCC and related to immune infiltration. The mutation landscape of ccRCC gene showed that the frequency of SETD2 mutation was 12.5%, ranking fourth in somatic mutation frequency. Among patients with ccRCC, the prognosis in the SETD2 high expression group was better than that in the SETD2 low expression group, and the prognosis of patients in the high immune infiltration group was better than that in the low immune infiltration group. Conclusion High expression of SETD2 can increase the infiltration of immune cells and its killing effect on tumor in ccRCC patients, thus playing a positive role in the prognosis of patients.