Abstract: Objective To characterize the antimicrobial resistance to ciprofloxacin in Salmonella isolates from diarrhea cases in Guangdong Province from 2009 to 2013. Methods All Salmonella strains isolated by ESS project between 2009 and 2013 were serotyped. Antimicrobial resistances to ciprofloxacin and nalidixic acid were determined by disk diffusion method and main serotypes resistant to ciprofloxacin were molecular typed by PFGE. Results In all 2 939 Salmonella strains isolated from diarrhea cases, 253 (8.61%) were resistant to ciprofloxacin and 665 (22.63%) were intermediately resistant to ciprofloxacin. Patients aged less than 7 years accounted for 73.52%（186/253）of total patients carrying the resistant strains and 76.84%（511/665）of the all patients with moderately sensitive strains, respectively. Increasing trends of resistance to ciprofloxacin were observed from 2009 to 2013（P<0.01）. Drug resistant strains isolated from cities of Dongguan, Foshan, Guangzhou, Zhongshan, and Zhuhai accounted for 86.96% (220/253) of the total strains of the province. Salmonella typhimurium, Salmonella 4,5,12:i:,Salmonella enterica,and Salmonella stanley,and Salmonella Derby were major serotypes among the resistant strains. The PFGE patterns of resistance strains from the predominant serotypes had different clonal lineage and showed significant genetic diversity. Conclusion The resistance to ciprofloxacin in isolates of Salmonella typhi was low in Guangdong Province, but gradually increasing from 2009 to 2012. The PFGE typing analysis appeared high genetic diversity in resistant strains.