In this study, we have identified Ran that interacts with and is deubiquitinated by USP13 through MS-based screening, and pharmacological inhibition of USP13 by Spautin-1 synergizes with Dox or CTX to induce ferroptosis in DLBCL possibly via the USP13-Ran signaling. This evidence concerns the gene RAN and diffuse large B-cell lymphoma.