Thursday will mark Horford's fifth missed game of the season and his first since Dec. 13 against the New Orleans Pelicans.
The Sixers are a perfect 4-0 without Horford this season, and they are 1-0 against the Hawks in 2019-20.
Horford joined the Sixers as a free agent in July after spending the previous three seasons with the Boston Celtics. He's looked solid so far with 12.5 points, 6.7 rebounds and 4.0 assists per game, though his 45.1 shooting percentage is the worst of his career.
The Celtics used caution with Horford late last season after he missed seven games in December due to patellofemoral pain syndrome in his left knee. The five-time All-Star sat out four of the final 10 regular-season games in 2018-19.
The 76ers are built to win right now with a loaded lineup that includes Horford, Joel Embiid, Ben Simmons, Tobias Harris and Josh Richardson, although Richardson is currently on the shelf with a hamstring injury.
Head coach Brett Brown has the luxury of limiting Horford's time on the court now because of that group, but the Sixers will need him at full strength to reach their championship ceiling.
With Horford out Thursday, much of the interior offensive and defensive responsibilities will land on Embiid's shoulders. Forward James Ennis III and center Kyle O'Quinn could see increased playing time as well.
Even without Horford, the 76ers should be favored to beat a 12-36 Hawks team that is last in the Eastern Conference.