Objective To analyze the single resistance and multiple resistance situation of of Helicobacter pylori (Hp) in Qingd‐ao area to commonly used antibacterial drugs and to investigate the mutation characteristics of drug‐related resistant genes .Methods Hp was isolated from the mucosal samples of gastric antrum .The agar diffusion test was used to determine the susceptibility of Hp to clarithromycin ,levofloxacin and metronidazole .The 23s rRNA of clarithromycin resistance gene ,gyrA of levofloxacin resistance gene and rdxA of metronidazole resistance gene were amplified by using PCR ,after the PCR products sequencing ,the sequence com‐parative analysis was performed by the ClustalW2 software .Results The drug susceptibility test results found that the single re‐sistance rates of 134 strains of clinically isolated Hp to clarithromycin ,levofloxacin and metronidazole were 40 .3% ,34 .3% and 43 .3% ,respectively .Only 17 .9% of Hp strains were susceptible to these 3 kinds of antibacterial drug ;the multi‐drug resistance rate was 29 .9% ,triple drug resistance rate was 9 .0% ;furthermore ,the double resistance rate of levofloxacin plus metronidazole was significantly lower than that of clarithromycin plus levofloxacin ,the difference was statistically significant(3 .0% vs .10 .4% ,χ2 = 5 .96 ,P=0 .015) .The drug resistance genes sequence analyses showed that the commonest mutation locus was A2143G (77 . 8% ) ,the commonest mode of gyrA gene mutation was N87K(78 .3% ) ,and which of rdxA gene was nucleotide insertion into loci 20/32 ,generating the frameshift mutation with the mutation rate of 44 .8% .Conclusion The multi‐drug resistance rate of Hp is high in Qingdao area .The effective antibacterial drugs should be selected according to the drug susceptibility test results .Levofloxa‐cin could serve as the first line drug for the eradication therapy scheme in this area .