Display omitted •Hydrophilic and hydrophobic cavities were both used to co-load VC and βC.•The stability of βC was improved after co-loading VC and βC in liposomes.•The release kinetics and mechanisms of βC from L-βC and L-VC-βC were studied. Vitamin C (VC) and β-Carotene (βC) were selected to produce co-encapsulated liposomes using hydrophilic and hydrophobic cavities simultaneously by ethanol injection method. The results of liposomal structure characterized by particle size, polydispersity index, zeta-potential and transmission electron microscope showed that the microstructure of all liposomal samples was spherical without adhesion or break and the size of VC-βC-loaded liposome (L-VC-βC) was bigger than VC-loaded liposome (L-VC) or βC-loaded liposome (L-βC). The encapsulation efficiency (EE) of VC in L-VC-βC was significantly higher than that in L-VC, and the EE of βC in L-VC-βC had no significant change compared with that in L-βC. The free radical scavenging rate of L-VC-βC was significantly higher than that of L-βC, while it had no significant change compared with that of L-VC. In addition, the storage stability of βC in L-VC-βC improved greatly compared with that in L-βC. Furthermore, the zero order model was applied to understand the release kinetics of βC from L-βC and L-VC-βC in the stomach, whereas the Korsmeyr-Peppas model was chosen to describe the release of βC from two types of liposome in small intestine and their release mechanisms were mainly dominated by Fickian diffusion. It was significant to provide a new idea for using hydrophilic and hydrophobic cavities simultaneously in liposomes to design the multicomponent nutrient delivery system.