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Ineffectiveness of anticancer drugs is frequently observed in cancer chemotherapy. The resistance of tumor cells to various cytotoxic drugs is defined as multidrug resistance(MDR). The purpose of our present study was to investigate the inhibit effects of L1EPO synthesized by our group on P-glycoprotein(P-gp)-mediated multidrug resistance(MDR)in K562/A02 cells. Both the cytotoxicity of the compound and its ability to inhibit the K562/A02 cells were determined with SRB assay. Morphologic apoptosis was detected by Hochest33342 staining assay. RT-PCR was used to detect mdr-1 gene transcription and the Western blot assay was used to assess P-gp expression. Interestingly，We found K562/A02 cell line was rendered resistant toward Adriamycin but not towards L1EPO when compared with the parental cells. And L1EPO could down regulated mdr-1 gene，and reduced the expression of P-gp and displayed a perfect dose dependent. Moreover，it had lesscytotoxicity in human normal cell lines(fibroblast，VEC)，GI50>10μmol/L. Consequently，L1EPO has the potential to overcomes P-glycoprotein-mediated Multidrug Resistance in K562/A02 Cell Line.