Objective: To find out whether silymarin could affect the mRNA and protein levels of CYP3A4,CYP2C9, CYP2C19, CYP2D6 and CYP2E1 in HepG2 cell line.Methods: Expressive levels of CYP3A4, CYP2C9, CYP2C19, CYP2D6 and CYP2E1 mRNA were determind in HepG2 cells treated by DMSO 0.1%(v/v) (control) and silymarin (5 μM, 10 μM, 20 μM, 40 μM, 80 μM) for 24 hours and 48 hours using RT-PCR.Expressive levels of CYP3A4 and CYP2C9 protein were determined in HepG2 cells treated by DMSO 0.1% (v/v) (control) and silymarin (5 μM, 10 μM, 20 μM, 40 μM, 80 μM) for 24 hours and 48 hours using western-blot.Results: Silymarin can significantly inhibit the expression of CYP3A4 mRNA after HepG2 cells were treated for 48 hours,and the inhibition effect is concentration dependent.We can also find a decline of CYP3A4 mRNA level after 24-hour silymarin treatment,which is of statistic significance at concentration of 40 μM;Silymarin can also significantly inhibit the expression of CYP2C9 mRNA after HepG2 cells were treated for both 24 and 48 hours.The inhibition effect is concentration dependent and more significant for 48 hours.Silymarins effects on CYP2C19,CYP2D6 and CYP2E1 were not observed.Silymarin can significantly inhibit the expression of CYP3A4 protein after HepG2 cells were treated for for both 24 and 48 hours, and the inhibition effect is concentration dependent, and is of most significance at concentration of 80 μM;Silymarin can also significantly inhibit the expression of CYP2C9 protein after HepG2 cells were treated both for 24 and 48 hours.The inhibition effect is concentration dependent and more significant for 48 hours.Conclusion: Silymarin can significantly inhibit the expression of CYP3A4 and CYP2C9, while has no effect on the expression of CYP2C19, CYP2D6 and CYP2E1 in HepG2 cells.The effects of silymarin on CYP3A4 and CYP2C9 varied with different concentrations of silymarin and treated periods.