Achieving　a　high　encapsulation　efficiency　and　loading　capacity　of　proteins　in　lecithin-based　liposomes　has　always　been　a　challenge.　Here,　we　use　Flash　Nano-Precipitation　(FNP)　to　produce　liposomes　and　investigated　the　encapsulation　of　model　protein　(Bovine　Serum　Albumin,　BSA).　Through　rapid　turbulent　mixing,　we　obtained　liposomes　with　small　size,　low　polydispersity,　and　good　batch　repeatability　at　a　high　production　rate.　We　demonstrated　that　the　bilayer　of　liposomes　prepared　solely　using　lecithin　was　defective,　which　led　to　the　fusion,　and　increased　size　and　polydispersity.　When　cholesterol　was　added　to　reach　a　lecithin-to-cholesterol　molar　ratio　of　5:3,　a　compact　bilayer　formed　to　effectively　inhibit　liposome　fusion.　The　encapsulation　efficiency　and　loading　capacity　of　BSA　was　as　high　as　∼　68%　and　∼　6%　in　lecithin-cholesterol　liposome,　respectively,　far　exceeding　the　values　reported　in　the　literature.　Further　study　by　Quartz　Crystal　Microbalance　with　Dissipation　(QCM-D)　revealed　that　the　highly　effective　encapsulation　was　due　to　the　rapid　mutual　adsorption　between　BSA　and　defective/curved　lecithin　double　layers　during　the　liposome　formation.　Such　rapid　mutual　adsorption　leads　to　the　layer-by-layer　assembly　and　formation　of　onion-like　compact　liposome　structure　as　revealed　by　Cryo-TEM.　This　simple　FNP　method　provides　a　scalable　manufacturing　approach　for　liposomes　with　efficient　protein　encapsulation.　The　revealed　adsorption　mechanism　between　protein　and　lecithin　bilayers　could　also　serve　as　a　guide　for　similar　studies.　©　2022　Elsevier　Inc.