The invention discloses a preparation method of a nano vacant-shell spherical hydrotalcite and belongs to the field of inorganic nano materials. The preparation method comprises steps of: first, preparing a silica microballoon and an alumina monohydrate sol; dipping the prepared silica microballoons in the alumina monohydrate sol for several times to obtain an alumina monohydrate wrapped silica composite microballoon with a core-shell structure; putting the obtained composite microballoon in a solution containing divalent metal salt, and crystallizing at a certain temperature to obtain the vacant-shell spherical hydrotalcite. The invention first realizes the preparation of a three-dimensional vacant-shell hydrotalcite and expands preparation method of the hydrotalcite materials. The prepared vacant-shell hydrotalcite has a controllable nano size, and an increased specific surface area due to the three-dimensional vacant-shell structure and the cavity.