Chasing a fifth continental title, Al Hilal SFC booked its Round of 16 spot with three matches to spare and will aim to finish as the League Stage winner.
Al Hilal went into the break level on 16 points with fellow Saudi Arabian side Al Ahli Saudi FC but top of the West Zone standings with a better goal difference.
It has been firing on all cylinders in the Saudi Pro League and looks capable of winning the continental title after suffering a semi-final heartbreak last season against eventual champion Al Ain FC of the UAE.
Al Hilal's confidence will be further boosted by the fact that it has only lost once to Persepolis in nine previous meetings on the continental stage.
Persepolis, on the other hand, can't afford to slip up as its hold on a knockout stage spot is flimsy, at best.
Sitting in sixth on six points before the break, the Iran side is in danger of being overtaken by the sides below the team and desperately needs a win to stay ahead.
The odds will be against Persepolis as the Iranian giant has not won its last five meetings with Saudi Arabian sides, including not scoring in the previous four games.
The match will be held at the Kingdom Arena in Riyadh.