Enterobacter infections pose a huge threat to animals, including humans. It is particularly important to develop drugs that specifically inhibit Enterobacter. In the present study, a C-type lectin named Pc LecE, which was widely distributed in Procambarus clarkii , could specifically reduce the proportions of Enterobacter and Mycoplasma in the hemolymph. Pc LecE showed specific antibacterial activity to Enterobacter in vitro and bacterial clearance activity to Enterobacter in vivo. Pc LecE alleviated the intestine damage in crayfish caused by Enterobacter cloacae. Pc LecE inhibits its proliferation, promotes its phagocytosis by hemocytes, and improves the survival rate of crayfish under E. cloacae infection. The specific inhibition of Enterobacter by Pc LecE might provide new insight into the regulation of immune homeostasis by C-type lectins and the preparation of Enterobacter -specific drugs. • Pc LecE could specifically reduce the proportions of Enterobacter and Mycoplasma in the hemolymph. • Pc LecE was upregulated after Enterobacter cloacae infection. • Pc LecE could specifically inhibiting the proliferation of Enterobacter in vitro. [ABSTRACT FROM AUTHOR]