Hydrophobically-modified hydroxypropylmethylcellulose (HM-HPMC) is a thickener with a long hydrophobic alkyl side chain. In this study, we investigated the gelation ability and rheological properties of a liposome/HM-HPMC mixed solution. The liposome suspension and the HM-HPMC aqueous solution each had low viscosities, but the viscosity increased rapidly when they were mixed. This is thought to be due to the formation of a 3D network structure caused by the hydrophobic group of HM-HPMC penetrating into the liposomal bilayer membrane, crosslinking the liposomes together. This hypothesis was supported by the fact that gelation did not occur when hydroxypropylmethylcellulose without a hydrophobic group was used. The viscosity of the liposome/HM-HPMC mixed solution decreased rapidly when a shear was applied, but immediately returned to the original gel state when the shear was removed, indicating a reversible reaction. When a strong shear is applied, the hydrophobic group of HM-HPMC detaches from the liposome. When the shear is removed, the liposome is again cross-linked by HM-HPMC. From these results, it was revealed that liposome cross-linked gels can be prepared when HM-HPMC is used.