[Objective]To study the effects of oridonin on Bel-7402/Sora cell proliferation,apoptosis,cycle and phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT)signaling pathway.[Methods]The concentration gradient increasing method was used to establish Bel-7402/Sora drug-resistant cell line.Cell counting kit-8(CCK-8)method was used to detect cell proliferation inhibition rate and calculate cell resistance reversal index,flow cytometry was used to detect the cell apoptosis and cell cycle,Real-time quantitative polymerase chain reaction(RT-PCR)method was used to detect mRNA expression level of PI3K,AKT and mammalian target of rapamycin(mTOR),Western blot method was used to detect PI3K,AKT,mTOR protein expression levels.[Results]Compared with blank control group,oridonin with final concentrations of 4,8,16,32,64 μmol·L-1 had a better proliferation inhibition on Bel-7402/Sora cells(P<0.05,P<0.01),and the effect was dependent on concentration.The resistance reversal index of oridonin on Bel-7402/Sora cells is 2.024.Compared with blank control group,the early,late and total apoptosis rate of oridonin group were significantly increased(P<0.01,P<0.05);compared with oridonin group,the early and total apoptosis rate of oridonin jointed Sorafenib group were significantly increased(P<0.05).Compared with blank control group,the proportion of G2 phase cells of oridonin group was significantly increased(P<0.01);compared with oridonin group,the proportion of G1 phases cells of oridonin jointed Sorafenib group was significantly increased,and G2 phases cells was significantly decreased(P<0.01).Compared with blank control group,PI3K,AKT and mTOR mRNA expression levels of oridonin group were significantly reduced(P<0.01);compared with oridonin group,PI3K,AKT and mTOR mRNA expression levels of oridonin jointed Sorafenib group were significantly reduced(P<0.01).Compared with blank control group,PI3K and AKT protein expression levels of oridonin group were significantly reduced(P<0.01),and mTOR protein expression levels were no statistical significance(P>0.05);compared with oridonin group,AKT protein expression levels of oridonin jointed Sorafenib group were significantly reduced(P<0.01),PI3K,mTOR protein expression levels were no statistical significance(P>0.05).[Conclusion]Oridonin can inhibit cell proliferation of Bel-7402/Sora cell,induce apoptosis,hinder cycle progression and its anti-tumor mechanism may be related to intervene in the PI3K/AKT signaling pathway.