Hummels picked up an ankle injury during Saturday's 2-1 loss to Bayern Munich and has been ruled out for three weeks.
His absence will heap further misery on head coach Jurgen Klopp, who has watched his men flounder in the Bundesliga with six defeats and one draw coming in their last seven league encounters.
Dortmund subsequently sit 16th in the table, 17 points behind leaders Bayern.
It initially appeared Klopp's side may get back on track at the weekend when Marco Reus put them ahead against the champions.
But Robert Lewandowski returned to haunt his former club with a leveller before Arjen Robben's penalty earned Pep Guardiola's team all three points.
Dortmund welcome Galatasaray in the UEFA Champions League on Tuesday, with Klopp's side having found some consolation in Europe, winning all three matches in Group D.