Layered　double　hydroxide　(LDH)　materials　have　been　of　interest　as　the　noble　metal　substitutes　for　oxygen　evolution　reaction　(OER)　in　alkaline　media　though　their　intrinsically　inferior　electrocatalytic　activity.　Proper　cation　vacancy　engineering　of　LDH　is　an　effective　approach　for　improving　intrinsic　activity　during　catalytic　OER.　In　this　work,　the　in-situ　formation　of　cation　vacancies　in　LDH　nanosheets　(NiFeCoZnvac-LDH)　is　successfully　realized　by　partially　Zn　etching　from　medium-entropy　NiFeCoZn-LDH　precursor.　In-situ　Raman　analysis　and　DFT　calculations　uncover　that　the　introduction　of　metal　cation　vacancies　can　significantly　lower　the　generation　potential　of　the　surface　reconstruction　for　the　formation　of　abundant　high-valence　active　centers　and　optimize　the　adsorption/desorption　energy　of　oxygen-containing　intermediates,　thereby　boosting　catalytic　OER　activity.　As　a　proof　of　concept,　the　obtained　NiFeCoZnvac-LDH　catalyst　just　requires　a　low　overpotential　of　222　mV　to　reach　a　current　density　of　10　mA　cm-2　with　a　small　Tafel　slope　of　37.17　mV　dec-1.　Furthermore,　the　NiFeCoZnvac-LDH　electrode　takes　an　ultralow　potential　of　1.48　V　at　10　mA　cm-　2　in　practical　anion　exchange　membrane　electrolyzer　and　operate　stably　at　100　mA　cm-　2　for　long　period　without　obvious　activity　attenuation.　The　present　study　enables　the　development　of　LDH　catalysts　for　efficient　water　oxidation　using　a　simple　and　robust　approach.