Objective To study the L-carnosine induced apoptosis of human hepatocellular carcinoma HepG2 cells and its mechanism.Methods Human hepatocellular carcinoma HepG2 cells were cultured in vitro,then the cells in logarithmic phase were divided into 5 mM,20 mM,50 mM L-carnosine group and control group,treated with 5 mM,20 mM,50 mM L-carnosine and saline respectively.The proliferation of HepG2 cells was measured by CCK-8 assay after 24 hours and 48 hours treatment.The cell apoptosis and cell cycle were detected by flow cytometry after 48 hours treatment.The protein expression of Caspase-8,PI3K and Akt were detected by Western blot in each group after 48 hours treatment.Results CCK-8 and flow cytometry assay showed that both 20 mM and 50 mM L-carnosine treated group significantly inhibited the proliferation of HepG2 cells after 24 hours and 48 hours,and the inhibition were in a time and dose-dependent manner.Western blot revealed that the expressions of PI3K and Akt were down-regulated with the increase of L-carnosine concentration,while the expression of Caspase-8 was increased.Conclusion L-carnosine exhibits an inhibitory effect of the proliferation and promote apoptosis of human liver cancer cell line HepG2.The mechanism may be associated with the inhibition of the PI3K/Akt signaling pathway and activation of Caspase-8 signaling pathway.