Thaddeus Young added 17 points, Willie Green had 14 and Samuel Dalembert had 10 points and 17 rebounds for the Sixers, who won for the eighth time in nine games and moved back to .500 at 21-21.
Philadelphia beat New York for the third straight time, and has won 12 of 14 against the Knicks.
Nate Robinson scored 26 points, Tim Thomas added 24 and David Lee had 20 points and 10 rebounds for the Knicks, whose three-game winning streak ended. New York has not had a winning streak longer than three games this season.
The Sixers were 9-7 without Brand and even won seven consecutive games before losing 95-93 to the Dallas Mavericks last Monday.
Philadelphia was 11-14 before Brand was sidelined. He signed a five-year, $80 million contract in the offseason with the Sixers, and entered averaging 15.9 points and 9.8 rebounds in 23 games.
Despite Brand's return, New York kept it close with some clutch 3-point shooting. The Knicks, 15-of-32 from long range, led 98-95 with 5:27 remaining. But the Sixers scored nine straight - four free throws by Miller, two by Dalembert and a 3-pointer by Royal Ivey - to go ahead 104-98 with 4:06 left.
New York got within 108-106 on a 3-pointer by Thomas with 1:06 left, but Young came right back with a short jumper and Dalembert received a pass from Iguodala for a slam dunk to give the 76ers a 112-106 lead with 1:03 remaining.
The Knicks then scored four straight to close within 112-110 on a layup by Robinson, but could get no closer.
Philadelphia led by as many as 15 in the first half, but trailed 66-63 at halftime. The Knicks connected on 10 of 20 shots from 3-point range in the first half.
Notes: The Sixers honored the World Series champion Phillies. Closer Brad Lidge participated in a ceremonial opening tip, while Lidge, outfielder Shane Victorino and pitcher Ryan Madson also competed in a 3-point shooting contest at halftime. ... Eagles quarterback Donovan McNabb watched from a front-row seat and received a loud ovation from the crowd. Eagles WR DeSean Jackson was also in attendance. ... Fans held a moment of silence before the game for North Carolina State women's basketball Kay Yow, who died of breast cancer at the age of 66. ... Sixers F Reggie Evans was inactive with the flu. ... Knicks F Danilo Gallinari sat out with a sore lower back. ... Lee registered his 32nd double-double this season for the Knicks.
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