Kidney renal clear cell carcinoma (KIRC) is a main subtype of kidney cancers. Cuproptosis and ferroptosis are correlated with immune infiltration and prognosis in tumors. However, the role of Cuproptosis-related Ferroptosis genes (CRFGs) in KIRC has rarely been fully understood. Therefore, we constructed a prognostic signature based on different expression of CRFGs in KIRC. All raw data of this study were extracted from public TCGA datasets. Cuproptosis and Ferroptosis genes were collected from the previous research. Finally, a total of 36 significantly different CRFGs were identified from TCGA–KIRC cohort. Six-gene signature (TRIB3,SLC2A3,PML,CD44,CDKN2AandMIOX) was identified by LASSO Cox regression based on the significantly different CRFGs. The CRFGs signature was correlated with worse overall survival and the AUC was 0.750. Functional enrichment indicated that CRFGs were mainly enriched in metabolism, drug resistance, tumor immunity pathways. Besides, the IC50 and immune checkpoint differentially expressed between different groups. The proposed 6-CRFGs signature is a promising biomarker to predict clinical outcomes and therapeutic responses for KIRC patient.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40001-023-01137-z.