【Objective】 To explore the effects and the possible mechanism of RNA targeting membrane-bound prostaglandin E2 synthase l（mPGES- 1）on proliferation，apoptosis and drug resistance of leukemia cell line K562/A.【Methods】RNA  interference was used to inhibit the expression of mPGES-1 of K562/A cells. Four groups were set up as follows：untreated group（K562/A），negative control group after interference（K562/A-NC），group after interference（K562/ A-KD），and group after interference with exogenous PGE2（K562/A-KD+PGE2）.Cell viability was assessed by CCK-8 assay. Cell apoptosis was analyzed by flow cytometry. Concentration of PGE2 was detected by ELISA. Proteins expression was detected by western blot.【Results】The  expression of mPGES- 1 in K562/A cells was significantly down- regulated and the synthesis of PGE2 decreased（ < 0.000 1）after RNA interference. After RNA interference，the proliferation of K562/A cells was inhibited and apoptosis increased，and  the sensitivity to chemotherapy drugs was enhanced（P  < 0.05）. Meanwhile，the expression of β-catenin and MDR1 was decreased（ < 0.01）. Exogenous PGE2 could reverse the effect of RNA interference on proliferation ，apoptosis and drug sensitivity in K562/A cells（< 0.05），and up-regulate the expression of β-catenin and MDR1（< 0.01）. XAV939，an inhibitor of β-catenin，could down-regulate the expression of β- catenin and MDR1 in an dose- dependent pattern in K562/A cells（< 0.05）.【Conclusions】RNA interference of mPGES- 1 could inhibit proliferation，induce  apoptosis and reverse drug resistance in K562/A cells. The mechanism was related to reducing the synthesis of PGE2 and thus down- regulating the expression of β- catenin and MDR1. Wnt/β- catenin signal pathway may participate in the regulation of MDR1 by mPGES-1/PGE2.