Well-defined microcapsules with polyamide-polyurea as a hybrid shell have been described for biomedical applications. Interfacial polymerization method with surfactant and cosurfactant was developed for the preparation of the hybrid microcapsules. After reaction, centrifugation, and freeze drying processes, the polyamide-polyurea hybrid microcapsules with porous membranes were successfully fabricated. Compared with previous researches of the single polyamide or polyurea microcapsules, experimental data showed that the hybrid microcapsules have a thicker shell and excellent mechanical property. Various diameters and morphologies for the hybrid microcapsules can be obtained by changing the stirring rate, drying method, and surfactant content.