Abstract: Objective: To investigate the expression of multi-drug resistance-associated proteins (MDR) in Hepatocellular cancer cell line HepG2 and in different concentrations of sub-cell line of oxaliplatin (Oxal),and to study the mechanism of their resistance to Oxal.Methods: HepG2 multi-drug resistance sub-cell line was induced by increasing the concentration of Oxal progressively,and the drug resistance cell line 2.5 μg/ml HepG2/Oxal and 5.0 μg/ml HepG2/Oxal was successfully established.The mRNA expression of the MDR,the expression of multi-drug resistance related protein (MRP) and breast cancer resistance protein (BCRP) in the cell lines (HepG2/Oxal) of 2.5 μg/ml HepG2/Oxal and 5.0 μg/ml HepG2/Oxal were detected using RT-PCR,and the variability of the gene expression was verified by Western blot.Results: HepG2/Oxal drug resistance cell subseries with IC50 value of 15 and 25 times were successfully constructed.BCRP expression was positively correlated with HepG2 drug resistance at mRNA and the protein level.But MDR and MRP did not display significant high expression in the prophase drug resistance subseries;the expression of MDR and MRP increased along with the rise of drug resistance level.Conclusions: BCRP plays an important role in the acquired character resistance of HepG2 cell line to Oxal;the expression of MDR and MRP is not obvious at the prophase of the resistance,but increases with the rise of the resistance level.