In summary, this study identifies FBXO10 as a pivotal regulator governing FRMPD1-dependent hepatocellular carcinogenesis through the following key findings: Elevated FBXO10 expression shows a significant clinical association with poor prognosis in HCC patients; functional validation establishes its cancer-promoting function in liver malignancies, and mechanistically, FBXO10 directly triggers the K63-linked polyubiquitination of FRMPD1 to accelerate its proteasome-dependent degradation, while the FBXO10–FRMPD1 regulatory axis critically drives hepatoma cell proliferation. The gene discussed is FRMPD1; the disease is cancer.