Background <p>The diagnosis and treatment of prostate cancer (PCa) continue to encounter numerous. The specific regulatory mechanism is not yet clear. Studies have shown that miRNA plays a role in the progression of PCa. This research was the first to systematically explore the regulatory mechanism of the miR-26b-5p/ADAM17 pathway in PCa. It reveals the role of the “miR-26b-5p/ADAM17” signaling axis in inhibiting the malignant phenotype of PCa cells and the tumor inflammatory microenvironment.</p> Methods <p>This study recruited serum samples from 138 PCa patients and 138 healthy controls. RT-qPCR was employed to quantify mRNA expression. The interaction was validated using a dual-luciferase assay. Cell proliferation was assessed by the CCK-8 assay, while cell migration and invasion were evaluated via Transwell. Flow cytometry was utilized to measure cell apoptosis, and enzyme-linked immunosorbent assay (ELISA) was performed to determine inflammatory cytokines levels.</p> Results <p>miR-26b-5p was significantly downregulated in PCa. Its low expression was strongly correlated with poor prognosis, and it functioned as an independent protective prognostic factor. Functional experiments demonstrated that the overexpression of miR-26b-5p markedly suppressed proliferation, migration, and invasion while promoting apoptosis and inhibiting the secretion of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Mechanistically, miR-26b-5p exerted its anti-tumor effects by directly targeting and suppressing ADAM17 expression. Furthermore, the overexpression of ADAM17 partially reversed the tumor-suppressive and anti-inflammatory effects mediated by miR-26b-5p.</p> Conclusion <p>miR-26b-5p functioned in PCa by directly targeting ADAM17.</p>