To investigate the effect and possible mechanisms of polyphyllin G (PPG),a bioactive compound extracted from the Trillium tschonoskii Maxim,on human lymphoma cells,the present study used CCK-8 and cell counting assays to detect the proliferation inhibition.Flow cytometric and western blot assays were performed to assess apoptosis,autophagy and investigate the mechanism.The results indicated that PPG inhibited growth,promoted apoptosis and autophagy in Raji lymphoma cells.PPG significantly down-regulated the expression of cancerous inhibitor of protein phosphatase 2A (CIP2A).PPG increased the activity of protein phosphatase 2A (PP2A),a downstream molecule of CIP2A.And PP2A in turn inhibited the phosphorylation of Akt.Furthermore,the PP2A inhibitor okadaic acid antagonized the effect of PPG on cell proliferation,apoptosis,and autophagy.These results indicated that PP2A played a critical role in PPG induced apoptosis and autophagy by down-regulating CIP2A.Conclusively,the above results showed that PPG suppressed growth and promoted the apoptosis and autophagy of lymphoma cells via inhibiting CIP2A/PP2A/Akt signaling pathways.PPG is a potential anticancer drug for the treatment of lymphoma.