Cronobacter spp. are high acid resistance pathogens classified as Class A pathogens in powdered infant formula. Herein, we investigated the function of Cronobacter luxS in acid response. Results showed that luxS significantly increased the resistance to acid, demonstrating bacterial survival, bacterial morphology and biofilm formation. Furthermore, LuxS might enhance acid response by mediating the up‐regulation of 5‐methyltetrahydropteroyltriglutamate–homocysteine S‐methyltransferase and homocysteine S‐methyltransferase and the down‐regulation of methionine adenosyltransferase in the quorum sensing pathway. Therefore, the quorum sensing pathway mediated by luxS is the key control target for Cronobacter survival in acidic environments.