〔Abstract〕 Objective To investigate the role of CXCL12 on hepG2 cells apoptosis and its molecular mechanism. Methods hepG2 cells apoptosis was detected by flow cytometry(FCM), protein expression involving hepG2 apoptosis was detected by Western blot and laser scanning confocal microscopy(LSCM), protein expression of PI3 K/AKT signaling pathway was detected by Western blot. Results 100 ng/ml CXCL12 had an ability in inhibiting hepG2 cells apoptosis, down-regulating the protein expression of Bax, up-regulating the protein expression of Bcl-2, p-p85 and p-AKT(ser473), while had no effect on the protein expression of p110β, p85 and AKT. The inhibitor of PI3 K(LY294002) blocked the anti-apoptosis effect of CXCL12, increased the protein expression of Bax, decreased the protein expression of Bcl-2, p-p85 and p-AKT(ser473), while had no effect on the protein expression of p110β, p85 and AKT. Conclusion CXCL12 can increase the ratio of Bcl-2/Bax, inhibit hepG2 cells apoptosis, and the potential mechanism may be related to the activation of PI3 K/AKT signaling pathway.