Ursolic　acid　(UA)　is　a　food-plant-derived　natural　product　which　has　good　anticancer　activities　and　low　toxicity.　However,　the　poor　water　solubility　of　UA　limits　its　application　in　clinic.　To　address　this　issue,　we　developed　a　carrier-free　nanodrug　by　self-assembly　of　UA.　Here,　we　showed　that　UA　nanoparticles　(NPs)　have　a　near-spherical　shape　with　a　diameter　of　∼150　nm.　UA　NPs　exhibited　higher　antiproliferative　activity;　significantly　caused　apoptosis;　decreased　the　expression　of　COX-2/VEGFR2/VEGFA;　and　increased　the　immunostimulatory　activity　of　TNF-α,　IL-6,　and　IFN-β　and　decreased　the　activity　of　STAT-3　in　A549　cells　in　vitro.　Furthermore,　UA　NPs　could　inhibit　tumor　growth　and　have　the　ability　of　liver　protection　in　vivo.　More　importantly,　UA　NPs　could　significantly　improve　the　activation　of　CD4+　T-cells,　which　indicated　that　UA　NPs　have　the　potential　for　immunotherapy.　Overall,　a　carrier-free　UA　nanodrug　may　be　a　promising　drug　to　further　enhance　their　anticancer　efficacy　and　immune　function.　©　2018　American　Chemical　Society.