Abstract <p>Our objective is to reveal IBSP expression within clear cell renal cell carcinoma (ccRCC) and the mechanism behind it. IBSP expression and its clinical significance in ccRCC were analyzed using the TCGA dataset. Both Western blotting and immunohistochemistry were utilized to examine IBSP expressions in clinical ccRCC specimens. Moreover, CCK-8, Annexin V-FITC/PI, wound healing, and Transwell assays were utilized to determine IBSP’s role in ccRCC progression in vitro. In addition, Western blotting was deployed to ascertain levels of IBSP, PI3K/p-PI3K, and AKT/p-AKT. The TCGA database and our tissue data showcased that, unlike normal tissues, IBSP was significantly overexpressed in ccRCC tissues. Down-regulating IBSP reduces cell abilities to proliferate, migrate, and invade, besides promoting apoptosis in vitro. In vitro and in vivo, IBSP down-regulation inhibited ccRCC growth cells by suppressing PI3K/AKT phosphorylation. IBSP acts as a potential oncogene and could be a prognostic biomarker and therapeutic target for ccRCC. Furthermore, targeting IBSP may enhance existing treatment strategies, such as combining it with PI3K/AKT inhibitors to improve patient outcomes.</p> Graphical Abstract <p></p>