Provided are a long-acting prodrug of entecavir and a preparation method and application thereof. The prodrug of entecavir has the structure shown in formula I, and the compound can be released slowly, continuously, and stably and converted into an active drug, entecavir, in the body, thereby achieving the purpose of long-acting. The definitions of R1, R2, and R3 in formula I are as described in the specification.