In a repeat of his spectacular winner against the same opposition in February, Hulk unleashed a crunching left-foot shot which flew in for SIPG’s opener on 25 minutes.
Zhang Wei and Wu Lei were also on target before Oscar, Asia’s record signing, added the fourth to keep FC Seoul at bay after their strikes through Maurinho and Park Chu-Young.
It put SIPG through alongside Group F rivals Urawa Red Diamonds, while Thailand’s Muangthong United beat Brisbane Roar 3-0 to reach the knock-outs for the first time.
Xisco nodded Muangthong’s opener on 37 minutes, a goal that ended the involvement of Brisbane goalkeeper Jamie Young who suffered a deep gash to his forearm as he collided with the post.
Chanathip “Messi Jay” Songkrasin beat two defenders and rounded the replacement ‘keeper, Tomislav Bilic, on 83 minutes before Teerasil Dangda added a third just before time.
It meant the end of the road for Brisbane, who fielded an under-strength side as they build up to Sunday’s A-League semi-final against Melbourne Victory.
Earlier Urawa also eliminated Australian opposition as the J-League leaders swamped 2014 champions Western Sydney Wanderers 6-1.
Takahiro Sekine opened the scoring before Yoshiaki Komai set up Zlatan Ljubijankic and then Tadanari Lee for Urawa’s second and third before half-time.
The Wanderers pulled one back through Jumpei Kusukami but Rafael Silva grabbed two goals in eight minutes and then teed up Shinzo Koroki to complete the rout.
In Group E, Kashima Antlers ousted Ulsan Hyundai with a comprehensive 4-0 win as they reached the last 16 for the first time since 2011.
Ulsan made it to half-time goalless against Kashima but some calamitous defending saw them slip 3-0 down in the space of 15 second-half minutes.
Results
Ulsan Hyundai (KOR) 0 Kashima Antlers (JPN) 4 (Kanazaki 52, 67, Pedro Junior 54, Leo Silva 90)
Muangthong United (THA) 3 (Xisco 37, Chanathip 83, Teerasil 89) Brisbane Roar (AUS) 0
Urawa Red Diamonds (JPN) 6 (Sekine 14, Ljubijankic 18, Lee 43, Silva 71, 79, Koroki 90+4) Western Sydney Wanderers (AUS) 1 (Kusukami 66)
Shanghai SIPG (CHN) 4 (Hulk 25, Zhang Wei 30, Wu Lei 43, Oscar 74) FC Seoul (KOR) 2 (Maurinho 10, Park Chu-Young 70)