Herein, a nonreversible heat-induced supramolecular gel based on natural products was reported for the first time. This natural triterpenoid, fupenzic acid (FA), isolated from the roots of Rosa laevigata, was discovered to be capable of forming supramolecular gel spontaneously in 50 % ethanol-water solution induced by heating. Distinguished from the common thermosensitive gels, the FA-gel showed a distinctive nonreversible phase transition from the liquid to gel state upon heating. In this work, the entire gelation process of FA-gel induced by heating was recorded digitally by microrheology monitor. And a unique heat-induced gelation mechanism based on self-assembled FA has been proposed by using various experimental methods and molecular dynamics (MD) simulation. Its excellent injectability and stability were also demonstrated. Furthermore, the FA-gel had been evaluated to exhibit better anti-tumor activity and higher biosafety comparing with its equivalent free-drug, which opened up a new possibility to reinforce antitumor efficacy by using natural product gelator originated from traditional Chinese medicine (TCM) without any complicated chemical modifications.