Nanotechnology　has　emerged　as　an　ideal　approach　for　achieving　the　efficient　chemo　agent　delivery.　However,　the　potential　toxicity　and　unclear　internal　metabolism　of　most　nano-carriers　was　still　a　major　obstacle　for　the　clinical　application.　Herein,　a　novel　＂core-shell＂　co-assembly　carrier-free　nanosystem　was　constructed　based　on　natural　sources　of　ursolic　acid　(UA)　and　polyphenol　(EGCG)　with　the　EpCAM-aptamer　modification　for　hepatocellular　carcinoma　(HCC)　synergistic　treatment.　As　the　nature　products　derived　from　food-plant,　UA　and　EGCG　had　good　anticancer　activities　and　low　toxicity.　With　the　simple　and　＂green＂　method,　the　nanodrugs　had　the　advantages　of　good　stability,　pH-responsive　and　strong　penetration　of　tumor　tissues,　which　was　expected　to　increase　tumor　cellular　uptake,　long　circulation　and　effectively　avoid　the　potential　defects　of　traditional　carriers.　The　nanocomplex　exhibited　the　low　cytotoxicity　in　the　normal　cells　in　vitro,　good　biosafety　of　organic　tissues　and　efficient　tumor　accumulation　in　vivo.　Importantly,　UA　combined　with　EGCG　showed　the　immunotherapy　by　activating　the　innate　immunity　and　acquired　immunity　resulting　in　significant　synergistic　therapeutic　effect.　The　research　could　provide　new　ideas　for　the　research　and　development　of　self-assembly　delivery　system　in　the　future,　and　offer　effective　intervention　strategies　for　clinical　HCC　treatment.　(C)　2021　Chinese　Pharmaceutical　Association　and　Institute　of　Materia　Medica,　Chinese　Academy　of　Medical　Sciences.　Production　and　hosting　by　Elsevier　B.V.