Proteasome-mediated proteolysis is primarily understood through the lens of substrates modified with homotypic K48-linked ubiquitin chains. Recent studies suggest that K11/K48-branched ubiquitination acts as a rapid proteolysis signal, facilitating substrate turnover during cell cycle checkpoints or under protein unfolding stress. Using cryo-electron microscopy single particle reconstruction (cryo-EM SPR), we determined the structures of multiple functional states of the human 26S proteasome in complex with a substrate featuring a K11/K48-branched ubiquitin chain. Our findings reveal a distinct substrate binding groove on the 19S regulatory particle, involving several proteasomal subunits, including Rpn2, which recognizes K48-linked di-ubiquitin through a structural motif similar to that of the well-known ubiquitin receptor Rpn1. The branching point of K11/K48 is located on the proximal ubiquitin, enabling multivalent interactions that likely enhance substrate binding affinity. This mechanism underscores the role of K11/K48-branched ubiquitination in promoting rapid substrate turnover under specific cellular conditions.