SUMO1 interacts with and SUMOylates Lats1. Lats1 SUMOylation at K751 destabilizes the phosphorylated Lats1. Lats1 SUMOylation at K751 attenuates kinase activity and suppresses Hippo signaling. Lats1 SUMOylation at K751 attenuates its tumor-suppressor functions.