Abstract: Objective To investigate the quinolone resistance to Salmonella and mutation relevant to quinolone resistance in Guangdong Province. Methods We select four main Salmonella serovars from Non typhi Salmonella surveillance in Guangdong between 2010 and 2011 to determine the minimum inhibitory concentration of nalidixic acid and ciprofloxacin by semi quantitative susceptibility test and detect mutants in gyrA and parC by sequencing. Results Salmonella typhimurium, Salmonella I 4,5,12:i:-, Salmonella enteritidis, and Salmonella stanley from 2010 to 2011 were selected for the antimicrobial susceptibility test. We found 75.4% (374/496) of Salmonella were resistant to nalidixic acid, of which resistant rates of Salmonella typhimurium, Salmonella I 4,5,12:i:-, Salmonella enteritidis and Stanley salmonella to nalidixic acid were 82.5% (207/251), 84.0% (84/100), 79.5% (70/88), and 22.8% (13/57), respectively.5.4% of Salmonella were resistant to ciprofloxacin.8.0% of Salmonella typhimurium was resistant to ciprofloxacin, followed by Salmonella I 4,5,12:i:- (5.0%) and Salmonella enteritidis (2.3%). Mutants were detected in 71.7% of Salmonella typhimurium isolates.86.1% of the mutants were detected in gyrA and 37.2% in parC , and 23.3% in both genes. Locus mutation at Ser83 in gyrA was observed in 35.0% of the ciprofloxacin resistant isolates, 3.1% of intermediate isolates and 3.0% of the susceptible isolates (P<0.01). Locus mutation at Asp87 in gyrA was observed in 75.0% of the ciprofloxacin resistant isolates, 65.6% of intermediate isolates and 55.8% of the susceptible isolates (P>0.05). Arg was detected in all five isolates with mutants at Ser80 in parC. Nine isolates with Thr57 mutants in parC were all resistant to nalidixic acid. Conclusion Generally Salmonella isolates in Guangdong were highly resistant to nalidixic acid, but sensitive to ciprofloxacin. Mutants in gyrA and parC which might affect quinolone resistance in Salmonella isolates should be confirmed by further experiments.