VP3 is a T7-like phage and was used as one of the typing phages in a phage-biotyping scheme that has been used for the typing of Vibrio cholerae (V. cholerae) O1 biotype El Tor. We studied the receptors of V. cholerae necessary for the lytic propagation of VP3. Our data shows that VP3 can adsorpt to the surface of V. cholerae through the core oligosaccharide of lipopolysaccharides (LPS); while VP3 still binds to the core oligosaccharide mutant at a lower efficiency, we continued to construct the transposon mutant bank to find other bacterial surface components involved in VP3 infection. Our further research also found VC2436 gene product outer membrane protein TolC was identified as the second receptor involving in VP3’s host adsorption step. TolC specifically interacts with VP3’s tail fiber protein gene product (gp) 44，the C-terminal fragment gp44（451-753） was necessary for its interaction with TolC. We also found that TolC protein sequence was 100% conserved in all 108 of VP3-sensitive strains; while 96% (81/84) of TolC in VP3-resistant strains revealed two hypervariable regions (76-90 aa and 278-291aa) that were predicted to be located at the loops exposed to the cell surface. Interestingly, our study showed that TolCA78D or TolC290-291 alteration has the binding defect with gp44. All in all, our study highlights the importance of the core oligosaccharide and TolC in VP3’s adsorption step and provides the detailed insights into the VP3-V. cholerae interactions.