Corneocytes represents the main water reservoir of stratum comeum, and that ability intimately arises from their architecture and total composition. Here we describe a novel method for fabricating a microgel-in-liposome (M-i-L) structure consisting of a sodium hyaluronate microgel and a lipid membrane envelop in order to mimic comeocyte cell structures. The essence of our approach is to use a lecithin-based microemulsion with a very low interfacial tension between the water droplet and oil continuous phase. Using this emulsion enables us to stabilize a dispersion of microgel particles without phase separation or aggregation. The addition of excess water produced single-core or multicore microgel particles enveloped in a lipid layer. To demonstrate the applicability of this unique vesicle system, we encapsulated a high concentration of natural moisturizing factor (NMF) in the microgel core and investigated how the M-i-L structure affected the water retention in comparison with other control systems. We have observed that our M-i-L particles with the NMF in the core, which mimicked the comeocyte cell structure, showed an excellent ability to retain water in the system. This experimental result inspired us to investigate how comeocyte cells, which feature a lipid-enveloped hydrogel structure, provide such long-lasting hydration to the skin.