Spontaneous generation of DNA-enclosing liposomes from a DNAlipid blend film is investigated. The special properties of the lipid vesicles, namely, micrometer size, unilamellarity, and dense polymer encapsulation acquired by the dehydrationrehydration process, are physicochemically revealed. We found that the formation of giant unilamellar vesicles encapsulating DNAs are governed by micropatterns of the films, such as dots and network patterns. From the results, we proposed a plausible physical mechanism for the dehydrationrehydration process, making it possible to optimize the encapsulation of any agent.