Objective To study the effects of matrine (MAT) on the apoptosis and the expression of PEG10 in human hepatocarcinoma cell line HepG2. Methods MTT assay was used to determine the proliferation-inhibition activity by MAT to HepG2 cell. JC-1 staining was prepared to detect the change of mitochondrial membrane potential in HepG2 cells after MAT was given. RT-PCR and immunocytochemical method for detecting the PEG10 gene and protein expression levels were used. Results MAT could inhibit the HepG2 cell proliferation above the concentration of 0.125 mg/mL (different from above-->MAT ≥ 0.1 g/L) and in a concentration-dependent and time-dependent manner(P<0.01). JC-1 staining and flow cytometry detection showed that MAT can significantly decrease the mitochondrial membrane potential of HepG2 cells (P < 0.01). The RT-PCR and immunocytochemical staining results showed that 0.5 and 2.0 mg/ml (different from Chinese) MAT could reduce PEG10 gene and protein expression obviously. Conclusion MAT could decrease the expression level of PEG10 gene and inhibited cell proliferation,change the mitochondrial membrane potential and induce HepG2 cell apoptosis.