It was in the 27th minute of the match when Salem Al-Dawsari gave the hosts at Prince Faisal bin Fahd Stadium a valuable lead.
Al-Hilal’s French striker Bafetimbi Gomis scored twice in the 50th and 70th minute to put the result beyond doubt.
Al Hilal will lock horns with Al Nassr on Tuesday in an all-Saudi Arabian semi-final.
On Friday, Persepolis officially protested against a lack of proper coordination in holding training sessions, and allocating all stadium seats to Al Hilal.
The Iranian club has sent an official protest letter to the AFC.
Also on Wednesday, players and coaches of Persepolis had to head back home from Tehran Mehrabad Airport after their flight to Saudi Arabia was canceled because the kingdom failed to issue a permit for their flight. The team flew to Saudi Arabia on Thursday evening instead.