Background: Reliable biomarkers are critical for risk stratification and prognostic evaluation in kidney renal clear cell carcinoma (KIRC). Although NOTCH receptor 4 (NOTCH4) has been implicated in the prognosis of multiple cancers, its role in KIRC remains poorly understood. Aim: This study aimed to elucidate the role of NOTCH4 in KIRC through comprehensive bioinformatics analysis. Methods and Results: RNA sequencing data and clinical information for 21 tumor types, including KIRC, were retrieved from The Cancer Genome Atlas (TCGA). Pan-cancer analysis revealed elevated NOTCH4 expression in 9 malignancies, including KIRC. Paired t-tests confirmed significant NOTCH4 upregulation in KIRC tissues compared to adjacent normal tissues, and receiver operating characteristic (ROC) curve analysis demonstrated its diagnostic efficacy in distinguishing tumors from normal tissues. These findings were validated using Gene Expression Omnibus (GEO) datasets. KIRC patients from TCGA were stratified into NOTCH4 low- and high-expression groups. Baseline analysis revealed significant differences in gender, T classification, N classification, M classification, clinical stage, and histological grade between groups. Logistic regression confirmed associations between NOTCH4 expression and these clinical characteristics. Subgroup analysis revealed significantly lower NOTCH4 expression in male patients, tumors with T3–T4 classification, N1 classification, M1 classification, stage III–stage IV disease, and G3–G4 tumors. Kaplan-Meier survival analysis indicated that high NOTCH4 expression correlated with prolonged event-free survival and overall survival. Cox regression analyses identified age, M classification, and histological grade were independent prognostic factors. A prognostic nomogram integrating NOTCH4 expression and these independent prognostic factors effectively predicted overall survival. Immune infiltration analysis revealed significant correlations between NOTCH4 expression and endothelial cells, pericytes, macrophages and other immune-related populations. Conclusion: NOTCH4 serves as a promising prognostic biomarker in KIRC and a potential therapeutic target for immunotherapy via immune microenvironment modulation.