This paper studied the regulation mechanism on antibiotic resistance of LTTRs family protein XapR in Aeromonas hydrophila. The Minimum bactericidal concentration of Aeromonas hydrophila ATCC 7966 (wild-type strain) and Aeromonas hydrophila ATCC 7966 xapR gene deletion strain （ΔxapR） against 34 antibiotics were measured to evaluate the antibiotic resistance. Further， quantitative proteomics were used to investigate the effect of xapR deletion on the protein expression of Aeromonas hydrophila. The results showed that by contrast with wild-type strains in terms of antibiotics resistance， the minimum bactericidal concentration of cefamandole reduced by 2 times in ΔxapR. Subsequently， omics analysis showed that xapR could regulate bacterial carbon metabolism， TCA cycle and other pathways， and also closely related to the expressions of outer membrane protein， TonB， and ABC transport system. In conclusion， XapR can change the drug resistance of Aeromonas hydrophila by regulating the central metabolic pathway and multiple resistance genes.