The Saudi side are aiming for a fifth continental title, after triumphing in Asia's premier club competition last year with victory over South Korea's Pohang Steelers in the final.
Al Hilal's Group A clashes with Istiklol will be closely watched as the Tajik club beat the Saudis 4-1 during one of the teams' encounters in the group stages last year.
Al Rayyan of Qatar were also drawn in the same group.
In the east zone, two-time winners Urawa Red Diamonds from Japan will face Chinese Super League champions Shandong Taishan after both sides were drawn in Group F.
In Group I, Japan's Kawasaki Frontale, who last year won the J-League for the fourth time in five seasons, will meet eight-time Chinese Super League champions Guangzhou FC -- which is fighting for its future because of a debt crisis at owners China Evergrande.
And in Group H, two-time winners Jeonbuk Motors of South Korea face Japan's Yokohama F. Marinos.
The two-legged final of this year's 40-team tournament has been moved to 2023 to allow the region's national sides to prepare for the Qatar World Cup, which is being played in winter months.
The west zone knockout-stage matches will also take place in February 2023, while those for the east zone will wrap up in August this year.
Group A: Al Hilal (KSA), Istiklol (TJK), Al Rayyan (QAT), play-off winner
Group B: Al Jazira (UAE), Al Shabab (KSA), Mumbai City (IND), Air Force Club (IRQ)
Group C: Foolad Khouzestan (IRN), Shabab Al Ahli (UAE), Ahal FC (TKM), Al Gharafa (QAT)
Group D: Al Duhail (QAT), Sepahan FC (IRN), Pakhtakor (UZB), play-off winner
Group E: Al Sadd (QAT), Al Faisaly (KSA), Al Wehdat (JOR), play-off winner
Group F: Shandong Taishan (CHN), Urawa Red Diamonds (JPN), Lion City Sailors (SIN), play-off winner
Group G: BG Pathum (THA), Jeonnam Dragons (KOR), United City (PHI), Melbourne City (AUS)
Group H: Jeonbuk Motors (KOR), Yokohama F. Marinos (JPN), Hoang Anh Gia Lai (VIE), play-off winner
Group I: Kawasaki Frontale (JPN), Guangzhou FC (CHN), Johor Darul Ta'zim (MAS), play-off winner
Group J: Shanghai Port (CHN), Chiangrai United (THA), Kitchee (HKG), play-off winner