Purpose: Fluoroquinolone-resistant Shigella is considered a serious public health problem and has been put on the WHO global priority list of antibiotic-resistant bacteria. This study was aimed to investigate the fluoroquinolone resistance in Shigella and its relevant genetic mechanisms. Materials and Methods: Shigella isolates that were isolated from diarrheal patient's feces in Ningbo China from 2011 to 2018 were tested for susceptibility to ampicillin, gentamicin, tetracycline, nalidixic acid, ciprofloxacin, and cefotaxime. Genes related to quinolone resistance were amplified by PCR. Results: A total of 118 Shigella isolates were collected, including 76 S. flexneri isolates, 40 S. sonnei isolates, and 2 S. boydii isolates. Ciprofloxacin susceptibility test identified 10 (9%) susceptible, 65 (55%) intermediate, and 43 (36%) resistant isolates. Of 76 S. flexneri isolates, 37 were ciprofloxacin resistant, a prevalence significantly higher than 6 of 40 S. sonnei isolates (P=0.01). The isolates collected during 2014-2018 displayed a significant increase in the prevalence of ciprofloxacin resistance (P=0.05) than those collected during 2011-2013. All the ciprofloxacin-intermediate and resistant isolates had mutations of gyrA(S83L) and parC (S80I), whereas only the ciprofloxacin-resistant isolates had gyrA (D87N) mutation and qnrB gene. Additionally, 30% of the ciprofloxacin-resistant isolates were positive for aac(6')-Ib-cr gene. Conclusion: This study shows the currently increasing prevalence of ciprofloxacin resistance. The reduced fluoroquinolone susceptibility is highly associated with gyrA (S83L) and parC (S80I) mutations, while the fluoroquinolone resistance is highly associated with gyrA (D87N) mutation, qnrB gene and perhaps aac(6')-Ib-cr gene.