Herein, we design a novel folate receptor-targeting and ROS-responsive liposome co-encapsulating methotrexate and catalase to actively target to activated macrophages through folate receptor-mediated endocytosis and subsequently release the drug by oxygen-generation induced structural failure of liposome through catalyzed reaction between catalase and elevated intracellular H2O2 for RA treatment. Here, CAT is linked to rheumatoid arthritis.