Aminopeptidase-like 1 (NPEPL1) is part of the aminopeptidase group that plays a part in the event and advancement of various illnesses. Expression of NPEPL1 continues to be considered to be involved with prostate, breast, and colorectal cancers. However, the function and mechanism of NPEPL1 in obvious cell kidney cell carcinoma (ccRCC) are unclear. Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) databases were utilised to calculate the connection between clinicopathological features and NPEPL1 expression. Alterations in immune status and drug sensitivity with NPEPL1 expression were examined through the “CIBERSORT” function in R software. The outcomes discovered that NPEPL1 expression was upregulated in ccRCC tissues, with expression progressively growing with ccRCC stage and grade. Patients rich in NPEPL1 expression given an undesirable prognosis across different clinicopathological features. Univariate and multivariate Cox regression analyses established that aberrant NPEPL1 expression was a completely independent risk factor for ccRCC. The nomogram demonstrated that NPEPL1 expression improved the precision of predicting the prognosis of ccRCC patients. The Gene Ontology (GO) term enrichment analysis and also the Kyoto Encyclopedia of Genes and Genomes (KEGG) path analysis says NPEPL1 may engage in the introduction of ccRCC with the current-gated calcium funnel complex, funnel activity, cAMP signaling path, and oxytocin signaling path. The coexpression analysis discovered that NPEPL1 altered tumor characteristics by getting together with related genes. The “CIBERSORT” analysis demonstrated that elevated NPEPL1 expression was adopted by an enrichment of regulatory T cells and follicular assistant T cells within the microenvironment. The drug sensitivity analysis found patients rich in NPEPL1 expression were built with a greater take advantage of axitinib, cisplatin, and GSK429286A. To conclude, upregulation of NPEPL1 expression was involved with ccRCC prognosis and treatment. NPEPL1 could be utilized for a therapeutic target to steer clinical dosing.