The 28-year-old Cameroonian forward made 10-of-19 from the floor and 13-of-15 from the free throw line while adding eight rebounds, five assists, two blocked shots and a steal for host Toronto.
The 76ers still lead the Raptors 3-1 in the best-of-seven first round series, which continues on Monday in Philadelphia. The series winner will face either Miami or Atlanta in the second round.
No team has ever recovered from a 3-0 deficit to win an NBA playoff series.
Philadelphia star centre Joel Embiid, the NBA scoring leader from Cameroon, was nagged by a right thumb injury despite producing 21 points and eight rebounds.
The Raptors were also hit by injuries, NBA Rookie of the Year Scottie Barnes tweaking a sprained left ankle and Fred VanVleet leaving in the second quarter with a left hip injury.
“He’s going to need some work,” Raptors coach Nick Nurse said of VanVleet. “He has been banged around good and gone out there and played some serious minutes. I’m sure he was frustrated.”
Siakam scored 15 points in the fourth quarter, holding off a Sixers fightback attempt in the final minutes, and Gary Trent Jr added 24 points for the Raptors.
James Harden led Philadelphia with 22 points while Tobias Harris added 15 points and 11 rebounds.
The Sixers have not swept a best-of-seven series since beating Milwaukee in the second round of the 1985 NBA playoffs.
Embiid, who averaged 27.7 points and 13.0 rebounds a game in the first three games, started despite the sore thumb, which Sixers coach Doc Rivers said could not be made worse by his playing.
VanVleet left with the Raptors in a 20-6 run that produced a 50-38 Toronto lead.
Philadelphia charged back within 54-49 at halftime and pulled level at 54-54 early in the third quarter, but could not grab the lead, trailing 80-77 entering the fourth before Siakam took over. (AFP)