To study the biology of hepatocellular carcinoma arerestrained through PI3K/AKt signaling pathways and targetedby tumor infiltrating macrophages.Methods: Mononuclear cellswere isolated from healthy adult peripheral blood by densitygradient centrifugation and induced with IL - 4 forselective activation of macrophagesin vitro.PI3K - siRNA andAKT – siRNA were transfected to hepatocellular carcinomacell line HepG2 respectively by lipofectermine 3000, andthen cultivate with selective activation of macrophages (M2)for 48 hour. PI3K and Akt mRNA expression level in livercancer HepG2 cells were detected with real-time fluorescentquantitative PCR. Results: After transfection, PI3K, and AktmRNA level were significantly decreased. In vitromicroenvironment of liver cancer, M2 can... significantlyincrease levels of PI3K, and Akt mRNA levels in HepG2 celllines, and can significantly promote the HepG2 cellproliferation ability (P< 0.05) after co-culture with M2 for24 hours. Conclusion: Tumor associated macrophages canpromote liver cancer cell proliferation through PI3K/Aktsignaling pathway. If changing the microenvironment of livercancer or specific inhibition of PI3K/Akt signaling pathwaycan also control the malignant biological behavior oftumors.