The invention provides neopentane beta-cyclodextrin hydroxypropyl tetraether and a preparation method and application thereof. The neopentane beta-cyclodextrin hydroxypropyl tetraether is a tetrapod compound, structurally comprises four beta-cyclodextrin groups, is high in beta-cyclodextrin group cavity proportion, can form a supermolecule clathrate compound with polymer or surfactant in drilling fluid, is high in high temperature resistance, good in salt resistance and stable in rheological property, can have an excellent filter loss lowering effect under the downhole high temperature condition and is promising in application prospect.