Nearly three dozen LAPD officers responded to the Oceanwide Plaza complex just before 2 p.m. Tuesday to search for vandalism suspects.
Details surrounding the four arrests were not immediately released.
Trespassers last week were seen spraying graffiti on the exterior of the building, leaving floor after floor tagged on several sides.
Taggers graffiti 27 floors of vacant high-rise in downtown LA
The empty three-tower complex is located near Crypto.com Arena and L.A. Live.
Construction work on Oceanwide Plaza stopped in October 2020 after the project's China-based developer ran out of money.
Last week, L.A. City Councilmember Kevin de León introduced a motion to clean up the graffiti.