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Salmonella Thompson is a prevalent foodborne pathogen and a major threat to food safety and public health. This study aims to reveal the dissemination mechanism of S. Thompson with co-resistance to ceftriaxone and ciprofloxacin. In this study, 181 S. Thompson isolates were obtained from a retrospective screening on 2118 serotyped Salmonella isolates from foods and patients, which were disseminated in 12 of 16 districts in Shanghai, China. A total of 10 (5.5 %) S. Thompson isolates exhibited resistance to ceftriaxone (MIC ranging from 8 to 32 μg/mL) and ciprofloxacin (MIC ranging from 2 to 8 μg/mL). The AmpC β-lactamase gene bla CMY-2 and plasmid-mediated quinolone resistance (PMQR) genes of qnr S and qep A were identified in the 9 isolates. Conjugation results showed that the co-transfer of bla CMY-2 , qnr S, and qep A occurred on the IncC plasmids with sizes of ∼150 (n = 8) or ∼138 (n = 1) kbp. Three typical modules of IS Ecp1 - bla CMY-2 - blc-sugE , IS 26 -IS 15DIV-qnr S-IS Kpn19 , and IS CR3 - qep A-intl1 were identified in an ST3 IncC plasmid pSH11G0791. Phylogenetic analysis indicated that IncC plasmids evolved into Lineages 1, 2, and 3. IncC plasmids from China including pSH11G0791 in this study fell into Lineage 1 with those from the USA, suggesting their close genotype relationship. In conclusion, to our knowledge, it is the first report of the co-existence of bla CMY-2 , qnr S, and qep A in IncC plasmids, and the conjugational transfer contributed to their dissemination in S. Thompson. These findings underline further challenges for the prevention and treatment of Enterobacteriaceae infections posed by IncC plasmids bearing bla CMY-2 , qnr S, and qep A. • Ceftriaxone and ciprofloxacin co-resistance was found in Salmonella Thompson. • Co-transfer of blaCMY-2, qnrS and qepA occurred on the IncC plasmids. • ISEcp1-blaCMY-2-blc-sugE, IS26-IS15DIV-qnrS-ISKpn19 and ISCR3-qepA-intl1 were found. • IncC plasmids from China fell into Lineage 1 with those from the USA. [ABSTRACT FROM AUTHOR]