Abstract： Objective To study the the role of berberine(BBR)in the regulation of efflux pump genes hefABC in mul-ti-drug resistant(MDR)strains of Helicobacter pylori(Hp).Methods ①Hp clinical isolates were tested the minimum in-hibitory concentration for amoxicillin,levofloxacin,clarithromycin and metronidazole by E-test method.,in which sensitive strains and MDR strains were screened.②The expression quantities diffenrence of efflux pump genes hefABC between MDR group and sensitive group were detected by Real-time fluorescent quantitative polymerase chain reaction(RT-PCR).③The MIC values of berberine against MDR strains were determined by agar two-fold dilution method.After the MDR strains were cultured at 1/2 MIC concentration of berberine in liquid for 5 generations,RT-PCR was used to detect the mRNA expression difference of the efflux pump genes before and after the addition of berberine.Results ①A total of sixty Hp strains were isolated and screened including fifteen sensitive strains and twelve MDR strains.②The expression quantities of hefA、hefB in the MDR group are significantly higher than that in the sensitive group(P<0.05).There are no high expressions of hefC be-tween two groups(P<0.05).③The expression quantities of Hp0605,Hp0606 of MDR group after the effects of berberine re-markably decrease,compared with that before treated with berberine,and the difference has statistical significance.Conclusions①Multi-drug resistance of H.pylori is related to the high expression of efflux pump genes of Hp0605,Hp0606.②Berberine can inhibit drug resistance in some MDR strains by down-regulating the expression of efflux pump genes hefA and hefB.