Abstract IL-33 is associated with the induction of Th2-type immunity, however it has recently gained attention for its role in boosting Th1-type immunity and CD8+ T cell function. We have discovered that IL-33 can induce robust antitumor effect through a CD8+ T cell dependent mechanism. Systemic administration of recombinant IL-33 (rIL-33) alone was sufficient to inhibit growth of established tumors in multiple mouse tumor models. Notably, rIL-33 treatment promoted antitumor CD8+ T cell expansion and effector function. Mechanistically, rIL-33 therapy primarily and directly targets dendritic cells in tumor bearing mice, thereby restores CTL activity by increasing antigen cross-presentation within the tumor microenvironment. Furthermore, agonist activation of CD40, which is induced by rIL-33 treatment, stabilized and induced regression of established tumors. Our study has elucidated the potential use of rIL-33 as a novel immunotherapy option for the treatment of established cancers.